Drug: Cardura

CARDURA® (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: CARDURA (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. CARDURA is available as colored tablets for oral use and contains 1 mg (white), 2 mg (yellow), 4 mg (orange) and 8 mg (green) of doxazosin as the free base. The inactive ingredients for all tablets are: microcrystalline cellulose, lactose, sodium starch glycolate, magnesium stearate and sodium lauryl sulfate. The 2 mg tablet contains D & C yellow 10 and FD & C yellow 6; the 4 mg tablet contains FD & C yellow 6; the 8 mg tablet contains FD & C blue 10 and D & C yellow 10.

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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 CARDURA in doses of 1–16 mg in hypertensives and 0.5–8 mg in normotensives. The adverse events when the incidence in the CARDURA 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
Body System (N=665) (N=300) BODY AS A WHOLE   Back Pain 1.80% 2.00%   Chest Pain 1.20% 0.70%   Fatigue 8.0%* 1.70%   Headache 9.90% 9.00%   Influenza-like Symptoms 1.10% 1.00%   Pain 2.00% 1.00% CARDIOVASCULAR SYSTEM   Hypotension 1.7%* 0.00%   Palpitation 1.20% 0.30% DIGESTIVE SYSTEM   Abdominal Pain 2.40% 2.00%   Diarrhea 2.30% 2.00%   Dyspepsia 1.70% 1.70%   Nausea 1.50% 0.70% METABOLIC AND NUTRITIONAL DISORDERS   Edema 2.7%* 0.70% NERVOUS SYSTEM   Dizziness† 15.6%* 9.00%   Mouth Dry 1.40% 0.30%   Somnolence 3.00% 1.00% RESPIRATORY SYSTEM   Dyspnea 2.6%* 0.30%   Respiratory Disorder 1.10% 0.70% SPECIAL SENSES   Vision Abnormal 1.40% 0.70% UROGENITAL SYSTEM   Impotence 1.10% 1.00%   Urinary Tract Infection 1.40% 2.30% SKIN & APPENDAGES   Sweating Increased 1.10% 1.00% PSYCHIATRIC DISORDERS   Anxiety 1.10% 0.30%   Insomnia 1.20% 0.30% *p ≤ 0.05 for treatment differences
†Includes vertigo In these placebo-controlled studies of 665 CARDURA 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 (CARDURA 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 CARDURA were mild. Hypertension CARDURA 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 CARDURA 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 1–16 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
(N=339) PLACEBO
(N=336) CARDIOVASCULAR SYSTEM   Dizziness 19% 9%   Vertigo 2% 1%   Postural Hypotension 0.30% 0%   Edema 4% 3%   Palpitation 2% 3%   Arrhythmia 1% 0%   Hypotension 1% 0%   Tachycardia 0.30% 1%   Peripheral Ischemia 0.30% 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% 0.30% PSYCHIATRIC   Somnolence 5% 1%   Nervousness 2% 2%   Depression 1% 1%   Insomnia 1% 1%   Sexual Dysfunction 2% 1% CARDIOVASCULAR SYSTEM   Dizziness 19% 9%   Vertigo 2% 1%   Postural Hypotension 0.30% 0%   Edema 4% 3%   Palpitation 2% 3%   Arrhythmia 1% 0%   Hypotension 1% 0%   Tachycardia 0.30% 1%   Peripheral Ischemia 0.30% 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% 0.30% PSYCHIATRIC   Somnolence 5% 1%   Nervousness 2% 2%   Depression 1% 1%   Insomnia 1% 1%   Sexual Dysfunction 2% 1% 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. CARDURA 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. CARDURA 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. Read the Cardura (doxazosin mesylate) Side Effects Center for a complete guide to possible side effectsLearn More »

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DOSAGE MUST BE INDIVIDUALIZED. The initial dosage of CARDURA in patients with hypertension and/or BPH is 1 mg given once daily in the a.m. or p.m. This starting dose is intended to minimize the frequency of postural hypotension and first-dose syncope associated with CARDURA. Postural effects are most likely to occur between 2 and 6 hours after a dose. Therefore, blood pressure measurements should be taken during this time period after the first dose and with each increase in dose. If CARDURA administration is discontinued for several days, therapy should be restarted using the initial dosing regimen. Concomitant administration of CARDURA with a PDE-5 inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension; therefore, PDE-5 inhibitor therapy should be initiated at the lowest dose in patients taking CARDURA.
  1. BENIGN PROSTATIC HYPERPLASIA 1–8 mg once daily. The initial dosage of CARDURA is 1 mg, given once daily in the a.m. or p.m. Depending on the individual patient's urodynamics and BPH symptomatology, dosage may then be increased to 2 mg and thereafter to 4 mg and 8 mg once daily, the maximum recommended dose for BPH. The recommended titration interval is 1–2 weeks. Blood pressure should be evaluated routinely in these patients.
  2. HYPERTENSION 1–16 mg once daily. The initial dosage of CARDURA is 1 mg given once daily. Depending on the individual patient's standing blood pressure response (based on measurements taken at 2–6 hours post-dose and 24 hours post-dose), dosage may then be increased to 2 mg and thereafter if necessary to 4 mg, 8 mg and 16 mg to achieve the desired reduction in blood pressure. Increases in dose beyond 4 mg increase the likelihood of excessive postural effects, including syncope, postural dizziness/vertigo and postural hypotension. At a titrated dose of 16 mg once daily, the frequency of postural effects is about 12% compared to 3% for placebo.

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Most (98%) of plasma doxazosin is protein bound. In vitro data in human plasma indicate that CARDURA has no effect on protein binding of digoxin, warfarin, phenytoin, or indomethacin. There is no information on the effect of other highly plasma protein-bound drugs on doxazosin binding. CARDURA has been administered without any evidence of an adverse drug interaction to patients receiving thiazide diuretics, beta-blocking agents, and nonsteroidal anti-inflammatory drugs. In a placebo-controlled trial in normal volunteers, the administration of a single 1 mg dose of doxazosin on day 1 of a four-day regimen of oral cimetidine (400 mg twice daily) resulted in a 10% increase in mean AUC of doxazosin (p=0.006), and a slight but not statistically significant increase in mean Cmax and mean half-life of doxazosin. The clinical significance of this increase in doxazosin AUC is unknown. In clinical trials, CARDURA tablets have been administered to patients on a variety of concomitant medications; while no formal interaction studies have been conducted, no interactions were observed. CARDURA tablets have been used with the following drugs or drug classes: 1) analgesic/anti-inflammatory (e.g., acetaminophen, aspirin, codeine and codeine combinations, ibuprofen, indomethacin); 2) antibiotics (e.g., erythromycin, trimethoprim and sulfamethoxazole, amoxicillin); 3) antihistamines (e.g., chlorpheniramine); 4) cardiovascular agents (e.g., atenolol, hydrochlorothiazide, propranolol); 5) corticosteroids; 6) gastrointestinal agents (e.g., antacids); 7) hypoglycemics and endocrine drugs; 8) sedatives and tranquilizers (e.g., diazepam); 9) cold and flu remedies. Concomitant administration of CARDURA with a phosphodiesterase-5 (PDE-5) inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension (see DOSAGE AND ADMINISTRATION). Cardiac Toxicity in Animals An increased incidence of myocardial necrosis or fibrosis was displayed by Sprague-Dawley rats after 6 months of dietary administration at concentrations calculated to provide 80 mg doxazosin/kg/day, and after 12 months of dietary administration at concentrations calculated to provide 40 mg doxazosin/kg/day (AUC exposure in rats 8 times the human AUC exposure with a 12 mg/day therapeutic dose). Myocardial fibrosis was observed in both rats and mice treated in the same manner with 40 mg doxazosin/kg/day for 18 months (exposure 8 times human AUC exposure in rats and somewhat equivalent to human Cmax exposure in mice). No cardiotoxicity was observed at lower doses (up to 10 or 20 mg/kg/day, depending on the study) in either species. These lesions were not observed after 12 months of oral dosing in dogs at maximum doses of 20 mg/kg/day [maximum plasma concentrations (Cmax) in dogs 14 times the Cmax exposure in humans receiving a 12 mg/day therapeutic dose] and in Wistar rats at doses of 100 mg/kg/day (Cmax exposures 15 times human Cmax exposure with a 12 mg/day therapeutic dose). There is no evidence that similar lesions occur in humans. Read the Cardura Drug Interactions Center for a complete guide to possible interactions Learn More »

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Benign Prostatic Hyperplasia (BPH) CARDURA is 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). CARDURA may be used in all BPH patients whether hypertensive or normotensive. In patients with hypertension and BPH, both conditions were effectively treated with CARDURA monotherapy. CARDURA provides rapid improvement in symptoms and urinary flow rate in 66–71% of patients. Sustained improvements with CARDURA were seen in patients treated for up to 14 weeks in double-blind studies and up to 2 years in open-label studies. Hypertension CARDURA is 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. CARDURA may be used alone or in combination with diuretics, beta-adrenergic blocking agents, calcium channel blockers, or angiotensin-converting enzyme inhibitors.

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CARDURA is contraindicated in patients with a known sensitivity to quinazolines (e.g., prazosin, terazosin), doxazosin, or any of the inert ingredients.Last reviewed on RxList: 11/22/2013
This monograph has been modified to include the generic and brand name in many instances.

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Experience with CARDURA overdosage is limited. Two adolescents, who each intentionally ingested 40 mg CARDURA 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 CARDURA 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 CARDURA and was reported to have been drowsy. A 32-year-old female with chronic renal failure, epilepsy, and depression intentionally ingested 60 mg CARDURA (blood level = 0.9 μg/mL; normal values in hypertensives = 0.02 μg/mL); death was attributed to a grand mal seizure resulting from hypotension. A 39-year-old female who ingested 70 mg CARDURA, alcohol, and Dalmane® (flurazepam) developed hypotension which responded to fluid therapy. The oral LD50 of 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.

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CARDURA (doxazosin mesylate) is available as colored tablets for oral administration. Each scored tablet contains doxazosin mesylate equivalent to 1 mg (white), 2 mg (yellow), 4 mg (orange) or 8 mg (green) of the active constituent, doxazosin. Bottle of 100 1 mg (NDC 0049-2750-66)
2 mg (NDC 0049-2760-66)
4 mg (NDC 0049-2770-66)
8 mg (NDC 0049-2780-66) Unit Dose Package of 100 1 mg (NDC 0049-2750-41)
2 mg (NDC 0049-2760-41)
4 mg (NDC 0049-2770-41)
8 mg (NDC 0049-2780-41) Recommended Storage Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Distributed by: Roerig, Division of Pfizer Inc, NY, NY 10017. Revised November 2013 Last reviewed on RxList: 11/22/2013
This monograph has been modified to include the generic and brand name in many instances.

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General Prostate Cancer 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 CARDURA. Cataract Surgery Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in some patients on or previously treated with alpha1 blockers. 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 alpha1 blocker therapy prior to cataract surgery. Orthostatic Hypotension While syncope is the most severe orthostatic effect of CARDURA, other symptoms of lowered blood pressure, such as dizziness, lightheadedness, or vertigo can occur, especially at initiation of therapy or at the time of dose increases. Hypertension These symptoms were common in clinical trials in hypertension, occurring in up to 23% of all patients treated and causing discontinuation of therapy in about 2%. In placebo-controlled titration trials in hypertension, orthostatic effects were minimized by beginning therapy at 1 mg per day and titrating every two weeks to 2, 4, or 8 mg per day. There was an increased frequency of orthostatic effects in patients given 8 mg or more, 10%, compared to 5% at 1–4 mg and 3% in the placebo group. Benign Prostatic Hyperplasia In placebo-controlled trials in BPH, the incidence of orthostatic hypotension with doxazosin was 0.3% and did not increase with increasing dosage (to 8 mg/day). The incidence of discontinuations due to hypotensive or orthostatic symptoms was 3.3% with doxazosin and 1% with placebo. The titration interval in these studies was one to two weeks. Patients in occupations in which orthostatic hypotension could be dangerous should be treated with particular caution. As alpha1 antagonists can cause orthostatic effects, it is important to evaluate standing blood pressure two minutes after standing, and patients should be advised to exercise care when arising from a supine or sitting position. If hypotension occurs, the patient should be placed in the supine position and, if this measure is inadequate, volume expansion with intravenous fluids or vasopressor therapy may be used. A transient hypotensive response is not a contraindication to further doses of CARDURA. Information for Patients (See PATIENT INFORMATION) Patients should be made aware 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. They should be cautioned to avoid situations where injury could result should syncope occur during initiation of doxazosin therapy. They should also be advised of the need to sit or lie down when symptoms of lowered blood pressure occur, although these symptoms are not always orthostatic, and to be careful when rising from a sitting or lying position. If dizziness, lightheadedness, or palpitations are bothersome, they should be reported to the physician, so that dose adjustment can be considered. Patients should also be told that drowsiness or somnolence can occur with CARDURA or any selective alpha1 adrenoceptor antagonist, requiring caution in people who must drive or operate heavy machinery. Patients should be advised about the possibility of priapism as a result of treatment with alpha1 antagonists. Patients should know that this adverse event is very rare. If they experience priapism, it should be brought to immediate medical attention, for, if not treated promptly, it can lead to permanent erectile dysfunction (impotence). Drug/Laboratory Test Interactions CARDURA does not affect the plasma concentration of prostate-specific antigen in patients treated for up to 3 years. Both doxazosin, an alpha1 inhibitor, and finasteride, a 5-alpha reductase inhibitor, are highly protein-bound and hepatically metabolized. There is no definitive controlled clinical experience on the concomitant use of alpha1 inhibitors and 5-alpha reductase inhibitors at this time. Impaired Liver Function CARDURA should be administered with caution to patients with evidence of impaired hepatic function, or to patients receiving drugs known to influence hepatic metabolism (see CLINICAL PHARMACOLOGY, Pharmacokinetics). Leukopenia/Neutropenia Analysis of hematologic data from hypertensive patients receiving CARDURA in controlled hypertension clinical trials showed that the mean WBC (N=474) and mean neutrophil counts (N=419) were decreased by 2.4% and 1.0%, respectively, compared to placebo, a phenomenon seen with other alpha-blocking drugs. In BPH patients, the incidence of clinically significant WBC abnormalities was 0.4% (2/459) with CARDURA and 0% (0/147) with placebo, with no statistically significant difference between the two treatment groups. A search through a data base of 2400 hypertensive patients and 665 BPH patients revealed 4 hypertensives in which drug-related neutropenia could not be ruled out and one BPH patient in which drug-related leukopenia could not be ruled out. Two hypertensives had a single low value on the last day of treatment. Two hypertensives had stable, non-progressive neutrophil counts in the 1000/mm³ range over periods of 20 and 40 weeks. One BPH patient had a decrease from a WBC count of 4800/mm³ to 2700/mm³ at the end of the study; there was no evidence of clinical impairment. In cases where follow-up was available, the WBCs and neutrophil counts returned to normal after discontinuation of CARDURA. No patients became symptomatic as a result of the low WBC or neutrophil counts. Carcinogenesis, Mutagenesis, Impairment of Fertility Chronic dietary administration (up to 24 months) of doxazosin mesylate at maximally tolerated doses of 40 mg/kg/day in rats and 120 mg/kg/day in mice revealed no evidence of carcinogenic potential. The highest doses evaluated in the rat and mouse studies are associated with AUCs (a measure of systemic exposure) that are 8 times and 4 times, respectively, the human AUC at a dose of 16 mg/day. Mutagenicity studies revealed no drug-or metabolite-related effects at either chromosomal or subchromosomal levels. Studies in rats showed reduced fertility in males treated with doxazosin at oral doses of 20 (but not 5 or 10) mg/kg/day, about 4 times the AUC exposures obtained with a 12 mg/day human dose. This effect was reversible within two weeks of drug withdrawal. There have been no reports of any effects of doxazosin on male fertility in humans. Pregnancy Teratogenic Effects - Pregnancy Category C Studies in pregnant rabbits and rats at daily oral doses of up to 41 and 20 mg/kg, respectively (plasma drug concentrations 10 and 4 times human Cmax and AUC exposures with a 12 mg/day therapeutic dose), have revealed no evidence of harm to the fetus. A dosage regimen of 82 mg/kg/day in the rabbit was associated with reduced fetal survival. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, CARDURA should be used during pregnancy only if clearly needed. Radioactivity was found to cross the placenta following oral administration of labelled doxazosin to pregnant rats. Nonteratogenic Effects In peri-postnatal studies in rats, postnatal development at maternal doses of 40 or 50 mg/kg/day of doxazosin (8 times human AUC exposure with a 12 mg/day therapeutic dose) was delayed, as evidenced by slower body weight gain and slightly later appearance of anatomical features and reflexes. Nursing Mothers Studies in lactating rats given a single oral dose of 1 mg/kg of [2-14C]-CARDURA indicate that doxazosin accumulates in rat breast milk with a maximum concentration about 20 times greater than the maternal plasma concentration. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when CARDURA is administered to a nursing mother. Pediatric Use The safety and effectiveness of CARDURA as an antihypertensive agent have not been established in children. Geriatric Use The safety and effectiveness profile of CARDURA in BPH was similar in the elderly (age ≥ 65 years) and younger (age < 65 years) patients. For Hypertension Clinical studies of CARDURA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. Last reviewed on RxList: 11/22/2013
This monograph has been modified to include the generic and brand name in many instances.

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