Information for the Patient
Cardura
Pharmacology
After oral administration of therapeutic doses of doxazosin, absorption occurs with peak blood levels at about 2 hours. Bioavailability is approximately 65%. Food has little or no effect on the bioavailability.
Approximately 98% of the circulating drug is bound to plasma proteins. Plasma elimination is biphasic with a terminal elimination half-life of about 22 hours. There is an accumulation of plasma doxazosin levels following steady state dosing, consistent with the terminal elimination half-life.
In a study of elderly hypertensive patients the pharmacokinetic parameters of doxazosin at steady state were similar to those observed in a previous study of young and elderly healthy subjects who received a single oral dose of doxazosin.
In a cross-over study in 24 normotensive subjects, the pharmacokinetics and safety of doxazosin were shown to be similar with morning and evening dosing regimens. Doxazosin may, therefore, be administered as a single daily morning or evening dose (see Dosage).
Doxazosin is extensively metabolized, mainly by O-demethylation of the quinazoline nucleus or hydroxylation of the benzodioxan moiety. Excretion is mainly via the feces with 9% of the dose excreted in urine as doxazosin (<0.5%) or metabolites. Less than 5% is excreted as the unchanged drug, mainly in the feces.
The disposition of doxazosin in patients with renal insufficiency is similar to that in patients with normal renal function. Only limited data are available in patients with liver impairment and on the effects of drugs known to influence hepatic metabolism (e.g., cimetidine) (see Precautions, Patients with Impaired Liver Function).
Indications
Hypertension: In the treatment of mild to moderate essential hypertension. It is employed in a general treatment program in association with a thiazide diuretic and/or other antihypertensive agents, as needed, for proper patient response.
Doxazosin may be tried as a sole therapy in those patients in whom treatment with other agents caused adverse effects or is inappropriate.
Benign Prostatic Hyperplasia (BPH): Doxazosin is also indicated for the treatment of symptoms of benign prostatic hyperplasia (BPH). The onset of effect is rapid, with improvement in peak flow and symptoms observed within 1 to 2 weeks. The effect on these variables was maintained over the entire study duration (up to 4 years). Doxazosin may be used in BPH patients who are either hypertensive or normotensive. While the reduction in blood pressure in normotensive patients with BPH is clinically insignificant, patients with hypertension and BPH have both conditions effectively treated with doxazosin monotherapy (see Dosage for dosage regimens).
A number of clinical conditions can mimic symptomatic BPH (i.e., stricture of urethra, stricture of bladder neck, urinary bladder stones, neurogenic bladder dysfunction secondary to diabetes, Parkinsonism, etc.). These conditions should therefore be ruled out before doxazosin therapy is initiated.
Precautions
Doxazosin is highly (98%) bound to plasma protein. In vitro data in human plasma indicates that doxazosin has no effect on protein binding of digoxin, warfarin, phenytoin or indomethacin.
Doxazosin has been administered to patients receiving thiazide diuretics, beta-adrenergic blocking agents and nonsteroidal anti-inflammatory drugs. No unexpected interactions were reported. An additive hypotensive effect was observed when doxazosin was coadministered with thiazide diuretics and beta-adrenergic blocking agents. There is limited experience with doxazosin in combination with ACE inhibitors or calcium channel blockers.
Digoxin: Serum digoxin concentrations were not affected by treatment with doxazosin.
Cimetidine: In a randomized, open-label, cross-over study in 22 male subjects, the single co-administration of 1 mg doxazosin with 400 mg b.i.d. cimetidine 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 effect of further administration of cimetidine has not been studied.
PDE-5 Inhibitors: Symptomatic hypotension has been reported during the concomitant use of PDE-5 inhibitors (e.g. sildenafil, tadalafil, vardenafil) and doxazosin (see Warnings).
Doxazosin should be used cautiously in elderly patients because of the possibility of postural hypotension. There was an age-related trend towards an increased incidence of postural hypotension and postural dizziness in elderly hypertensive patients treated with this drug.
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.
Myocardial fibrosis was observed in both rats and mice treated in the same manner with 40 mg doxazosin/kg/day for 18 months. 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 and Wistar rats at maximum doses of 20 and 100 mg/kg/day respectively. There is no evidence that similar lesions occur in humans.
Studies in lactating rats indicate that doxazosin accumulates in rat breast milk. It is not known whether this drug is excreted in human milk. Caution should be exercised when doxazosin is administered to a nursing mother and, in general, nursing should be interrupted.
The use of doxazosin is not recommended in children since safety and efficacy have not been established.
Doxazosin therapy does not modify the natural history of benign prostatic hyperplasia (BPH). It does not retard or stop the progression of BPH, nor does it improve urine flow sufficiently to significantly reduce the residual urine volume. However, significant reduction of the mean residual volume has been shown in patients with baseline residual volumes of >50 mL. The patient may continue to be at risk of developing urinary retention and other BPH complications during doxazosin therapy.
Long-term Safety and Efficacy: The long-term safety and efficacy (i.e., >4 years) have not yet been established for the use of doxazosin in the treatment of benign prostatic hyperplasia.
Prostatic Cancer: Carcinoma of the prostate and BPH cause many of the same symptoms. These two diseases frequently coexist. Therefore, patients thought to have BPH should be examined prior to starting doxazosin therapy to rule out the presence of carcinoma of the prostate.
Doxazosin should not be used in patients with PSA >10 ng/mL unless cancer of the prostate has been ruled out.
Patients with Impaired Liver Function: As with any drug wholly metabolized by the liver, doxazosin should be administered with caution to patients with evidence of impaired hepatic function or to patients receiving drugs known to influence hepatic metabolism.
Patients with Impaired Renal Function: The use of doxazosin in patients with impaired renal function requires careful monitoring. Clinical studies indicate that the disposition of doxazosin in patients with renal insufficiency is similar to that in patients with normal renal function, however, accumulation of the drug with chronic dosing may occur. Less than 10% of the dose of doxazosin is excreted in the urine as unchanged drug and metabolites.
Concomitant Conditions: Doxazosin should not be prescribed to patients with symptomatic BPH who have the following concomitant conditions:
Chronic urinary retention, high residual urine (over 200 mL), peak urine flow of 5 mL/s or less, history of prior prostatic surgery, chronic fibrous or granulomatous prostatitis, urethral stricture, history of pelvic irradiation, presence of prostatic calculi, presence of large median lobe of prostate, presence of calculi in urinary bladder, recent history of epididymitis, gross hematuria, presence of neurogenic bladder dysfunction (diabetes mellitus, parkinsonism, uninhibited neurogenic bladder, etc.), hydronephrosis, presence of carcinoma of the prostate. Nor should doxazosin be prescribed to patients having experienced a myocardial infarction, transient ischemic attacks, or cerebrovascular accident within the past 6 months.
There are no studies in pregnant women. Doxazosin is not recommended in pregnant women unless the potential benefit outweighs the potential risk to mother and fetus.
Doxazosin crosses the placental barrier.
Studies in pregnant rabbits and rats at daily oral doses of up to 40 and 20 mg/kg, respectively, have revealed no evidence of teratogenic effect. A dosage regimen of 82 mg/kg/day in the rabbit was associated with reduced fetal survival, an increase in embryomortality as well as increases in fetal and placental weights.
In peri- and postnatal studies in rats, postnatal development at maternal doses of 40 or 50 mg/kg/day of doxazosin was delayed as evidenced by slower body weight gain and a slightly later appearance of anatomical features and reflexes.
Supplied
Each white tablet, engraved ASTRA on one side and CARDURA with 1 on the other side, contains: doxazosin mesylate equivalent to doxazosin 1 mg. Nonmedicinal ingredients: lactose, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate and sodium starch glycolate. Opaque plastic (high density polyethylene) bottles of 100. Store at room temperature, 15 to 30°C.
Each white tablet, engraved ASTRA on one side and CARDURA with 2 on the other side, contains: doxazosin mesylate equivalent to doxazosin 2 mg. Nonmedicinal ingredients: lactose, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate and sodium starch glycolate. Opaque plastic (high density polyethylene) bottles of 100. Store at room temperature, 15 to 30°C.
Contraindications
Patients with a known sensitivity to doxazosin or quinazolines.
Warnings
Syncope and “First Dose” Effect: Doxazosin can cause marked hypotension, especially postural hypotension and syncope in association with the first dose or first few doses of therapy. A similar effect can occur if therapy is reinstated following interruption for more than a few doses. Postural effects are most likely to occur between 2 and 6 hours after dose.
In controlled studies of doxazosin the incidence of syncopal episodes was 0.7%. An initial dose of 1 mg/day resulted in a 4% incidence of postural side effects with no cases of syncope. In controlled clinical trials for BPH in normotensive patients, there was a 0.2% occurrence of syncope with doxazosin. In controlled trials in patients with both BPH and hypertension receiving doxazosin, the incidence of syncope was 0.8%.
The likelihood of syncopal episodes or excessive hypotension can be minimized by limiting the initial dose of doxazosin to 1 mg, by increasing the dosage slowly and by introducing any additional antihypertensive drugs into the patient's regimen with caution (see Dosage).
Patients should be advised of the possibility of syncopal and orthostatic symptoms, and to avoid driving or hazardous tasks for 24 hours: after the initial dose of doxazosin, after the dose is increased, and after interruption of therapy when treatment is resumed. They should be cautioned to avoid situations where injury could result should syncope occur.
If syncope occurs, the patient should be placed in the supine position. If this measure is inadequate, volume expansion with i.v. fluids or vasopressor therapy may be used. A transient hypotensive response is not a contraindication to further doses of doxazosin.
Orthostatic Hypotension: While syncope is the most severe orthostatic effect of doxazosin, other symptoms of lowered blood pressure such as dizziness, lightheadedness or vertigo can occur. These 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, there was an increased frequency of orthostatic effects in patients given 8 mg or more (10%) compared to patients given 1 to 4 mg (5%) or placebo (3%).
In placebo-controlled trials in BPH, the incidence of orthostatic hypotension with doxazosin was ≤1%. With maintenance doses of up to 8 mg/day in normotensive patients with BPH, the average decreases in both sitting and standing blood pressure were small: 5/2 mmHg with doxazosin and 1/1 mmHg with placebo.
Patients with occupations in which such events represent potential problems should be treated with particular caution.
Concomitant administration of doxazosin with a PDE-5 inhibitor such as sildenafil, tadalafil or vardenafil, should be used with caution as it may lead to symptomatic hypotension.
Patients should be advised of the need to lie down when symptoms of lowered blood pressure occur, and to be careful when arising from a 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 doxazosin, requiring caution in people who must drive or operate heavy machinery.
If hypotension occurs, place the patient in the recumbent position and institute supportive measures as necessary.
Priapism: Rarely (probably less frequently than once in every several thousand patients), α1-antagonists such as doxazosin have been associated with priapism. Because this condition can lead to permanent impotence if not promptly treated, patients should be advised about the seriousness of the condition.
Hematological Events: Analysis of hematologic data from patients receiving doxazosin in controlled clinical trials showed that the mean white blood cell (WBC) (n=474) and mean neutrophil counts (n=419) were decreased by 2.4% and 1.0% respectively, compared to placebo. A search through a data base of 2400 patients revealed 4 cases in which drug-related neutropenia could not be ruled out. Two had a single low value on the last day of treatment. Two had stable, nonprogressive neutrophil counts in the 1000/mm3 range over periods of 20 and 40 weeks. No patients became symptomatic as a result of the low WBC or neutrophil counts.
In BPH patients treated with doxazosin, the incidence of clinically significant WBC abnormalities was 0.4%.
In postmarketing experience, rare cases of hematopoietic events such as leukopenia and thrombocytopenia have been reported.
Hepatic Events: In postmarketing experience, rare cases of abnormal liver function tests, cholestasis, jaundice and hepatitis have been reported.
Peripheral Edema: Fluid retention resulting in weight gain may occur during doxazosin therapy. In placebo-controlled monotherapy trials, patients receiving doxazosin gained a mean of 0.6 kg compared to a mean loss of 0.1 kg for placebo-treated patients. The overall incidence of body weight gain reported as a side effect in controlled clinical trials was 0.8%.
Adverse Effects
Hypertension: Doxazosin has been administered to approximately 4 000 patients in clinical trials of whom 1 679 patients were included in controlled trials. The most serious adverse event occurring in the controlled clinical trials was syncope occurring in 0.7% of patients and resulting in a discontinuation rate of 0.2%.
The most frequent adverse events in controlled clinical trials were: headache (16.5%), fatigue/malaise (14.8%), dizziness (14.6%), postural dizziness (8.7%) and edema (6.6%). Discontinuation of doxazosin due to adverse events was required in 7% of patients.
Adverse events which occurred with an incidence of ≥1% in the controlled clinical trials in patients with mild to moderate essential hypertension were as shown in Table 1.
Table 1: CarduraAdverse Events | Adverse Event | Incidence (n=1679)
(%) |
| All Adverse Events | 49.0 |
| Headache | 16.5 |
| Fatigue | 14.8 |
| Dizziness | 14.6 |
| Postural Dizziness | 8.7 |
| Edema | 6.6 |
| Somnolence | 4.9 |
| Nausea | 3.9 |
| Dyspnea | 3.9 |
| Decrease in Platelets | 3.9 |
| Palpitation | 3.6 |
| Sexual Dysfunction | 3.5 |
| Dry Mouth | 3.4 |
| Vertigo | 3.0 |
| Rhinitis | 3.0 |
| Diarrhea | 2.9 |
| Chest Pain | 2.7 |
| Asthenia | 2.7 |
| Vision/Accommodation Abnormalities | 2.4 |
| Decrease in White Blood Cells | 2.4 |
| Anxiety/Nervousness | 2.3 |
| Insomnia | 2.2 |
| Dyspepsia | 2.1 |
| Rash | 1.7 |
| Paresthesia | 1.7 |
| Muscle Cramps | 1.7 |
| Tachycardia | 1.6 |
| Depression/Apathy | 1.6 |
| Hypoesthesia | 1.6 |
| Abdominal Pain | 1.6 |
| Decrease in Hematocrit | 1.6 |
| Increased Sweating | 1.4 |
| Flatulence | 1.4 |
| Decrease in Hemoglobin | 1.4 |
| Pain (general body) | 1.3 |
| Myalgia | 1.3 |
| Constipation | 1.3 |
| Conjunctivitis/Eye Pain | 1.2 |
| Micturition Frequency | 1.2 |
| Polyuria | 1.0 |
| Decrease in Neutrophil Count | 1.0 |
The following other adverse events occurred in hypertensive patients with an incidence of <1% in controlled clinical trials (n=1679): postural hypotension, arrhythmia, syncope, pruritus, arthralgia, agitation, flushing, tremor, paroniria, tinnitus, vomiting, epistaxis, sinusitis, bronchospasm/bronchitis, urinary incontinence, urinary disorder, face edema, weight increase, general edema, angina pectoris, peripheral ischemia, hypotension, paresis, twitching, migraine, amnesia, movement disorders, emotional lability, abnormal thinking, depersonalization, pallor, hypertonia, ataxia, thirst, gout, hypokalemia, lymphadenopathy, purpura, breast pain, alopecia, dry skin, eczema, taste perversion, photophobia, abnormal lacrimation, increased appetite, anorexia, fecal incontinence, coughing, pharyngitis, hot flushes, back pain, infection, fever/rigors and muscle weakness.
Benign Prostatic Hyperplasia: Doxazosin has been administered once daily to 665 both hypertensive and normotensive patients with BPH in controlled clinical trials. The most serious adverse event occurring in the controlled trials was syncope (0.5%).
The most frequent adverse events in controlled trials were dizziness (15.6%), headache (9.8%) and fatigue (8%).
Discontinuation rate of doxazosin due to adverse events was 9%.
Adverse events which occurred with an incidence of ≥1% in the controlled clinical trials in normotensive or hypertensive patients with BPH were as shown in Table 2.
Table 2: CarduraAdverse Events | Adverse Event | Incidence |
Short Terma
(n=665)
% | Long Termb
(n=450)
% |
| All Adverse Events | 45.0 | 66.0 |
| Dizziness | 15.6 | 20.7 |
| Headache | 9.8 | 12.2 |
| Fatigue | 8.0 | 11.6 |
| Somnolence | 3.0 | 4.9 |
| Edema | 2.7 | 4.9 |
| Dyspnea | 2.6 | <1 |
| Diarrhea | 2.3 | 3.8 |
| Abdominal Pain | 2.3 | 1.8 |
| Pain | 2.0 | 5.1 |
| Back Pain | 1.8 | 2.9 |
| Dyspepsia | 1.8 | 2.4 |
| Hypotension | 1.7 | 2.5 |
| Nausea | 1.5 | 3.1 |
| Dry Mouth | 1.4 | <1 |
| Abnormal Vision | 1.4 | 2.2 |
| Palpitation | 1.2 | 1.8 |
| Chest Pain | 1.2 | 3.8 |
| Insomnia | 1.2 | 1.3 |
| Urinary Tract Infection | 1.2 | 1.1 |
| Anxiety | 1.1 | <1 |
| Respiratory Disorder | 1.1 | 2.5 |
| Impotence | 1.1 | 4.9 |
| Increased Sweating | 1.1 | <1 |
| Leg Cramps | <1 | 1.6 |
| Hypertonia | <1 | 1.1 |
| Paresthesia | <1 | 1.1 |
| Tremor | — | 1.1 |
| Asthenia | <1 | 1.1 |
| Depression | <1 | 3.1 |
| Decreased Libido | <1 | 2.7 |
| Constipation | <1 | 1.3 |
| Prostatic Disorder | <1 | 1.8 |
| Ejaculation Failure | <1 | 1.1 |
| Urinary Retention | <1 | 1.6 |
| Dermatitis | — | 1.3 |
| Rash | <1 | 1.3 |
| Arthralgia | <1 | 1.3 |
| Arrhythmia | — | 1.1 |
| Myocardial Infarction | <1 | 1.3 |
| Hematuria | <1 | 1.8 |
| Tinnitus | <1 | 1.3 |
a. Placebo-controlled clinical trials; treated with doxazosin from 1 to 203 days.
b. Open label extension of 3 placebo-controlled clinical trials; treated for up to 50 months.
The following other adverse events occurred in normotensive or hypertensive patients with BPH with an incidence of <1% in short-term controlled clinical trials (n=665): tachycardia, angina, syncope, postural hypotension, pruritus, rash, myalgia, paresthesia, flushing, conjunctivitis, tinnitus, decreased libido, depression, nervousness, flatulence, rhinitis, epistaxis, carcinoma, dysuria, asthenia, influenza-like symptoms, viral infection, fever, weight increase, malaise, myocardial infarction, bradycardia, sudden death, pallor, hyperglycemia, gout, lymphadenopathy, prostatic disorder, ejaculation failure, epididymitis, dry skin, genital pruritus, urticaria, maculopapular rash, erythematous rash, aggravated psoriasis, eczema, hypoesthesia, hypertonia, leg cramps, confusion, speech disorder, ataxia, abnormal thinking, depersonalization, paroniria, emotional lability, impaired concentration, amnesia, earache, taste perversion, eye pain, visual field defect, cataract, melena, constipation, vomiting, gingivitis, increased appetite, coughing, bronchospasm, bronchitis, upper respiratory tract infection, sinusitis, pneumonia, urinary retention, micturition disorder, abnormal urine, renal pain, urinary incontinence, cystitis, arthritis, tendon disorder, arthralgia, hernia, rigors, hot flushes, allergy, sepsis, fungal infection, hematuria and subarachnoid hemorrhage.
The following other adverse events occurred in normotensive or hypertensive patients with BPH with an incidence of <1% in long-term controlled clinical trials (n=450): convulsions, encephalopathy, hypokinesia, migraine, fever, malaise, rigor, enlarged abdomen, allergic reaction/allergy, weight increase, nervousness, amnesia, anxiety, depersonalization, impaired concentration, abnormal thinking, flatulence, melena, vomiting, rectal hemorrhage, abnormal semen, tooth disorder, increased appetite, diverticulitis, esophagitis, gastric ulcer, tenesmus, tongue disorder, tooth hypoplasia, syncope, aneurysm, cardiac failure, abnormal ECG, hypertension, epistaxis, pharyngitis, rhinitis, bronchitis, pulmonary carcinoma, epididymitis, perineal pain, cystitis, dysuria, polyuria, urinary incontinence, oliguria, abnormal urine, increased sweating, seborrhea, maculopapular rash, skin disorder, nail disorder, photosensitivity reaction, pruritus, skin hypertrophy, urticaria, conjunctivitis, diplopia, eye abnormality, eye pain, myopia, visual field defect, myalgia, arthritis, polymyalgia rheumatica, atrial fibrillation, tachycardia, extra systoles, angina pectoris, myocardial ischemia, flushing, dry mouth, aggravated hypertension, sexual dysfunction, purpura, deafness, earache, cerebrovascular disorder/accident, intermittent claudication, carcinoma, herpes simplex, herpes zoster, fungal infection, otitis media, dehydration, hyperglycemia, hyperuricemia, cholelithiasis, AST increase, ALT increase and breast neoplasm.
Data from long-term (up to 50 months), open BPH studies (n=450) indicate higher rates of dizziness in younger hypertensive (27%) and normotensive (22%) patients, impotence in younger hypertensive (8%) patients, and discontinuation rates in patients due to adverse events (16.7%) compared to data from short-term placebo-controlled BPH studies (n=665).
Uncontrolled Trials and Postmarketing Experience: The following additional adverse events have also been reported in patients with essential hypertension and in normotensive or hypertensive patients with BPH: parosmia, renal calculus, priapism, ejaculation disorders such as retrograde ejaculation, jaundice, cholestasis and hepatitis.
Laboratory Abnormalities: No clinically relevant adverse effects were noted on serum potassium, serum glucose, uric acid, blood urea nitrogen or creatinine. Decreases in white blood cells, neutrophils, platelets (see Warnings), hemoglobin and hematocrit have been reported. Abnormal liver function tests have occurred.
Overdose
Should administration of doxazosin lead to hypotension, support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. If this measure is inadequate, shock should first be treated with volume expanders. If necessary, vasopressors should be used. Renal function should be monitored and supported as needed. As doxazosin is highly protein bound, dialysis may not be of benefit.
Dosage
Dosage must be individualized. Doxazosin may be administered either in the morning or in the evening.
The absorption of doxazosin is not affected by food.
When doxazosin is being added to the existing antihypertensive therapy, the patient should be carefully monitored for the occurrence of hypotension (see Warnings, Syncope and "First Dose" Effect). If a diuretic or other antihypertensive agent is being added to a doxazosin regimen, reducing the dose of doxazosin and retitration, with careful monitoring, may be necessary.
If doxazosin administration is discontinued for several days, or longer, therapy should be reinstituted using the initial dosing regimen.
Hypertension: 1 to 16 mg Once Daily: The initial dose of doxazosin in patients with hypertension is 1 mg given once daily and this dose should not be exceeded. This starting dose is intended to minimize postural hypotensive effects. The maximum reduction in blood pressure normally occurs between 2 and 6 hours after a dose.
The dose may be slowly increased to achieve the desired blood pressure response. The usual dose range is 1 to 8 mg once daily. The maximum recommended daily dose is 16 mg once daily.
Increases in dose beyond 4 mg increased 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.
Benign Prostatic Hyperplasia: 1 to 8 mg Once Daily: The initial dosage of doxazosin is 1 mg given once daily (see Warnings, Syncope and "First Dose" Effect). 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. The recommended titration interval is 1 to 2 weeks. Blood pressure should be evaluated routinely in these patients.
Doxazosin should be discontinued if the drug has been increased to the maximum tolerated dose and improvement in urinary flowmetry is less than 25% or if doxazosin side effects are more bothersome than BPH symptoms, or if the patient develops a urinary complication secondary to BPH while on doxazosin therapy.
