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Prazosin hydrochloride is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. Prazosin's efficacy in hypertensive patients appears to be similar to that of thiazide diuretics, β-adrenergic blocking agents, hydralazine, and centrally acting adrenergic inhibitors (e.g., clonidine, methyldopa). However, in one randomized, double-blind clinical study (the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]), doxazosin, an α1-blocker, was shown to be less effective in lowering mean systolic blood pressure (by about 2-3 mm Hg) than chlorthalidone, a thiazide-like diuretic. In order to achieve target blood pressure in hypertensive patients, use of doxazosin required additional hypotensive therapy more frequently than chlorthalidone. In addition, interim analysis (median follow-up: 3.3 years) of this study indicates that use of doxazosin in high-risk (at least 2 risk factors for coronary heart disease) hypertensive patients 55 years of age and older was associated with a higher risk of stroke and incidence of combined cardiovascular disease events (including twice the risk of congestive heart failure than use of chlorthalidone. Study investigators concluded that such increased risk of congestive heart failure could not have been caused by the relatively small difference in the mean target systolic blood pressure observed in patients receiving doxazosin compared with those receiving chlorthalidone. Therefore, based on these findings, the trial's Data Safety and Monitoring Board recommended that the α-blocker treatment arm be terminated prematurely. The remaining antihypertensive arms (e.g., calcium-channel blocking agents, angiotensin-converting enzyme [ACE] inhibitors, diuretics) and lipid-lowering (pravastatin vs usual care) components of the study subsequently were completed and reported.

Because of established clinical benefits (e.g., reductions in overall mortality and in adverse cardiovascular, cerebrovascular, and renal outcomes), ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics generally are considered the preferred drugs for the initial management of hypertension in adults. Although in the past α1-blockers such as prazosin were recommended as one of several classes of first-line antihypertensive therapy or as initial therapy in selected hypertensive patients (e.g., those with symptomatic prostatic hyperplasia), current antihypertensive and urology guidelines no longer recommend α1-blockers as preferred first-line therapy for any patients with hypertension, principally because of negative findings observed in ALLHAT. However, α1-blockers are effective antihypertensive drugs and many experts still consider their use appropriate for the management of resistant hypertension as a component of combination therapy. Although some experts state that an α1-blocker may be a useful component of antihypertensive treatment regimens in older men with coexisting benign prostatic hyperplasia (BPH), the American Urology Association (AUA) states that monotherapy with these drugs is not optimal in hypertensive patients with lower urinary tract symptoms (LUTS) or BPH and that such conditions should be managed separately .

The beneficial effects of α1-blockers on blood glucose and lipid concentrations may mitigate some of the adverse metabolic effects of diuretics, and α1-blockers may offer some advantage in patients with underlying lipoprotein disorders (e.g., hypercholesterolemia) or in those with lipoprotein abnormalities induced by other antihypertensive agents (e.g., thiazide diuretics). The possibility that geriatric patients may be more susceptible than younger patients to the postural hypotensive effects of α1-blockers should be considered in the selection of therapy. Blood pressure response to α1-blockers appears to be comparable in white and black patients.

Prazosin generally is most effective when used with a diuretic. The use of a diuretic may permit reduction of prazosin dosage. Prazosin has also been used with other hypotensive drugs, permitting a reduction in the dosage of each drug and, in some patients, minimizing adverse effects while maintaining blood pressure control. (See Drug Interactions: Diuretics and Hypotensive Agents.)

For further information on overall principles and expert recommendations for treatment of hypertension,

Benign Prostatic Hyperplasia

Prazosin has been used to reduce urinary obstruction and relieve associated manifestations (e.g., urinary hesitancy and/or urgency, nocturia) in patients with symptomatic benign prostatic hyperplasia (BPH, benign prostatic hypertrophy) but efficacy relative to other α1-blockers remains to be established. For patients who can tolerate the potential cardiovascular and other effects of α1-adrenergic blockade, the drug can effectively relieve mild to moderate obstructive manifestations in a substantial proportion of patients, at least in the short term, and may be a useful alternative to surgery, particularly in those who are awaiting or are unwilling to undergo surgical correction of the hyperplasia (e.g., via transurethral resection of the prostate [TURP]) or who are not candidates for such surgery.

Therapy with α1-blockers appears to be less effective in relieving irritative than obstructive symptomatology. In addition, therapy with the drugs generally can be expected to produce less subjective and objective improvement than prostatectomy, and periodic monitoring (e.g., performance of digital rectal examination, serum creatinine determinations, serum prostate specific antigen [PSA] assays) is indicated in these patients to detect and manage other potential complications of or conditions associated with BPH (e.g., obstructive uropathy, prostatic carcinoma). While symptomatic improvement has been observed in the short term in some patients receiving prazosin therapy, the long-term effects of α1-blockers on the need for surgery and on the frequency of developing BPH-associated complications such as acute urinary obstruction remain to be established. Currently available α1-adrenergic blockers (with the exception of prazosin, for which there are insufficient data to compare) are considered comparably effective.

Current evidence from principally uncontrolled, short-term studies suggests that the α1-selective adrenergic blocker prazosin produces beneficial effects in approximately 60-70% of treated patients without the degree of adverse effects associated with nonselective adrenergic blockers; alleviation of both obstructive and irritative manifestations of the hyperplasia has been reported in some patients with prazosin therapy. In a few placebo-controlled or comparative studies, therapy with prazosin in dosages of 1-9 mg daily (generally 2 mg twice daily) has improved urinary flow rates and reduced urinary frequency and nocturia in patients with BPH.

Combination therapy with an α1-blocker and 5α-reductase inhibitor (e.g., finasteride) has been more effective than therapy with either drug alone in preventing long-term BPH symptom progression; combined therapy also can reduce the risks of long-term acute urinary retention and the need for invasive therapy compared with α1-blocker monotherapy.

For additional information on the use of α1-blockers in the management of BPH,

Posttraumatic Stress Disorder

Prazosin has been used in the management of posttraumatic stress disorder (PTSD), particularly in combat veterans and in patients experiencing nighttime PTSD symptoms (e.g., nightmares, sleep disturbances). Nightmares and other sleep disturbances reportedly occur in about 70-87% of patients with PTSD; such patients often have decreased sleep efficiency because of more frequent nocturnal awakenings, as well as a higher incidence of other parasomnias and sleep-related breathing disorders compared with patients who have idiopathic nightmares.

Although selective serotonin-reuptake inhibitors (SSRIs; e.g., paroxetine, sertraline) generally have been considered the drugs of choice for the pharmacologic treatment of PTSD, they usually have not been effective in treating nighttime PTSD symptoms, which can be very disturbing and substantially interfere with the patient's quality of life. Atypical antipsychotic agents also have been studied in the treatment of PTSD and have been shown to reduce nighttime PTSD symptoms and may help reduce accompanying psychotic and other symptoms (e.g., agitation, irritability) in some patients; however, routine and long-term use of these drugs is discouraged by some clinicians because of the risk of clinically important adverse effects, such as weight gain and diabetes mellitus.

Clinical experience with prazosin in PTSD to date, which is mainly from small case series, case reports, retrospective or open-label studies, and several small randomized placebo-controlled studies, indicates that the drug is effective in suppressing or eliminating the nighttime sleep-related symptoms associated with PTSD. In several open-label and retrospective studies, prazosin therapy substantially improved trauma-related nightmares and reduced the severity of PTSD (as assessed by the recurrent distressing dreams item of the Clinician-Administered PTSD Scale [CAPS] and/or the Clinical Global Impression of Change [CGI-C] Scale, a 7-point clinician-rated assessment measuring overall PTSD severity and function).

In 2 randomized, double-blind, placebo-controlled trials conducted in combat veterans with PTSD, prazosin was found to be superior to placebo in reducing trauma-related nightmares and sleep disturbances. In the first study, 10 Vietnam combat veterans (mean age: 53 years) with chronic PTSD and severe trauma-related nightmares were randomized to receive prazosin or placebo with crossover to the opposite treatment arm occurring midway through the 20-week study. Prazosin was found to be more effective than placebo in reducing nightmares and sleep disturbances (assessed by CAPS) as well as improving overall PTSD severity and functional status (assessed by the CGI-C Scale). The second study, which was 8 weeks in duration, was conducted in a larger group of patients (40 US combat veterans; mean age: 56 years) with chronic PTSD, distressing trauma nightmares, and sleep disturbances. Compared with placebo, patients receiving prazosin in this study experienced substantially greater improvements in each of the 3 primary outcome measures addressing frequency and intensity of trauma-related nightmares and sleep quality used in this study (the CAPS recurrent distressing dreams item, the Pittsburgh Sleep Quality Index, and the CGI-C).

In a double-blind, placebo-controlled study in 13 patients with civilian trauma-related PTSD, prazosin reduced trauma-related nightmares, distressed awakenings, and total PTSD Checklist-Civilian scores; improved Clinical Global Impression of Improvement scores; and changed the PTSD Dream Rating Scale toward normal dreaming compared with placebo; the drug also improved objective measures of sleep (total sleep time, total REM sleep time, mean REM period duration) without changing sleep onset latency. In a historical prospective cohort study using retrospective chart review, the short-term effectiveness of prazosin (62 patients) and quetiapine (175 patients) in treating nighttime PTSD symptoms in combat veterans was found to be similar. However, long-term effectiveness (3-6 years) of prazosin was better compared with quetiapine; the quetiapine-treated patients were found to be more likely to discontinue therapy because of adverse effects than the prazosin-treated patients (approximately 35 and 18%, respectively). Prazosin therapy was generally found to be well tolerated when used in the treatment of PTSD-associated nightmares and other symptoms.

Some clinicians recommend prazosin as either first-line or alternative therapy when treating PTSD patients with prominent nighttime symptoms (e.g., nightmares, insomnia, sleep disturbances), particularly in combat veterans. Prazosin therapy could potentially be beneficial in some older PTSD patients who have hypertension and/or benign prostatic hyperplasia, since these conditions also may respond to therapy with the drug. Although preliminary findings have been very encouraging, larger, well controlled studies are needed to more fully define the role and optimum dosing of prazosin in the pharmacologic management of PTSD. In addition, further studies are needed to determine the safety and efficacy of prazosin in civilians with noncombat trauma-related PTSD and in the treatment of daytime symptoms associated with PTSD. Several controlled studies, including comparative and augmentation trials, are planned or currently underway to further evaluate prazosin in patients with this disorder.

For additional information on management of PTSD,

Other Uses

Prazosin has been effective in conjunction with cardiac glycosides and diuretics for the management of severe congestive heart failure, often producing improvements in cardiac function indexes and exercise tolerance. Although partial or complete tolerance to the hemodynamic effects of prazosin has reportedly developed rapidly in some patients, the attenuated response may be transient and/or corrected by dosage adjustment, by temporarily withdrawing the drug, and/or by the addition of an aldosterone antagonist (e.g., spironolactone) to the treatment regimen; acute hemodynamic attenuation does not preclude a beneficial hemodynamic response, especially during exercise. Most studies evaluating the long-term effects of prazosin have suggested that beneficial clinical and hemodynamic effects are sustained; however, conflicting results have been reported. Further studies are needed to determine the efficacy and role of prazosin for the long-term treatment of severe congestive heart failure.

Prazosin has been used with good results alone or in combination with a β-blocker for the preoperative management of the signs and symptoms of pheochromocytoma in a limited number of patients; however, these patients may be particularly susceptible to a marked hypotensive response to the initial dose of prazosin. Limited data also suggest that prazosin may be useful for the treatment of Raynaud's disease or phenomenon and ergotamine-induced peripheral ischemia.

Dosage and Administration


Prazosin hydrochloride is administered orally.


Dosage of prazosin hydrochloride is expressed in terms of prazosin and must be adjusted according to the patient's blood pressure response and tolerance.


Usual Dosage

For the management of hypertension, the usual initial adult dosage of prazosin is 1 mg given 2 or 3 times daily; higher doses should not be used for initial therapy, since initiation of therapy with doses in excess of 1 mg may cause syncope. (See Cautions: Postural Effects.) It has been suggested that syncopal episodes can be minimized by limiting the initial dose of the drug to 1 mg, by subsequently increasing dosage gradually, and by introducing other hypotensive agents into the patient's regimen cautiously. Dosage of prazosin may be gradually increased if necessary to a total dosage of 20 mg daily administered in divided doses. Higher dosages usually do not increase efficacy, but a few patients may benefit from up to 40 mg of prazosin daily. The usual maintenance dosage is 6-15 mg daily given in divided doses. For maintenance therapy, prazosin may be administered twice daily in some patients.

When other hypotensive agents or diuretics are added to existing prazosin therapy, the dosage of prazosin in adults should be reduced to 1 or 2 mg given 3 times daily and gradually increased according to the response and tolerance of the patient.

If prazosin is used for the management of hypertension in children, some experts recommend a usual initial dosage of 0.05-0.1 mg/kg daily given in 3 divided doses. Dosage may be increased as necessary to a maximum of 0.5 mg/kg daily given in 3 divided doses. For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients,

Blood Pressure Monitoring and Treatment Goals

Careful monitoring of blood pressure during initial titration or subsequent upward adjustment in dosage of prazosin is recommended.

The goal of hypertension management and prevention is to achieve and maintain optimal control of blood pressure; specific target levels of blood pressure should be individualized based on consideration of multiple factors, including patient age and comorbidities, and the currently available evidence from clinical studies.

For additional information on initiating and adjusting prazosin dosage in the management of hypertension,

Benign Prostatic Hyperplasia

In the treatment of benign prostatic hyperplasia, prazosin generally has been used in a dosage of 2 mg twice daily; however, dosages ranging from 1-9 mg daily also have been used.

Posttraumatic Stress Disorder

The optimum dosage regimen of prazosin for the management of posttraumatic stress disorder (PTSD) in adults has not been fully established. However, in clinical studies, prazosin usually was initiated at a dosage of 1 mg given at bedtime; the dosage was gradually increased (i.e., in 1- or 2-mg increments every few days or week) until an effective (i.e., nighttime symptoms associated with PTSD, such as nightmares and sleep disturbances, were substantially reduced) and well tolerated dosage was reached. Some clinicians recommend monitoring patients receiving prazosin for PTSD for first-dose syncope and orthostatic hypotension, particularly early in therapy. (See Cautions: Postural Effects and also see Cautions: Precautions and Contraindications.) In the available clinical studies, maintenance dosages ranging from 1 to 25 mg daily have been used. Some experts recommend a target maintenance dosage of 1-10 mg daily, while others recommend a higher target maintenance dosage of 2-20 mg daily. Although prazosin usually has been given once daily at bedtime, particularly when lower daily dosages have been used, some clinicians recommend a twice-daily regimen to help control daytime PTSD symptoms; further trials are needed to determine the optimal timing of doses for symptom control. Symptom relief appears to occur within several days to 2 weeks after beginning therapy with the drug.

Although the optimal duration of therapy has not been established, PTSD is often a chronic disorder and requires long-term therapy (i.e., for at least 1 to 2 years). Some PTSD patients have received the drug for up to 6 years. Because a rapid return of symptoms following prazosin discontinuance has been reported, some patients may require therapy indefinitely.

Dosage in Renal Impairment

For the management of hypertension in adults with renal failure, therapy with prazosin should be initiated with 1 mg twice daily. Patients with chronic renal failure may require only small doses of the drug.


Adverse effects occurring most frequently during prazosin hydrochloride therapy include dizziness, lightheadedness, headache, drowsiness, lack of energy, weakness, palpitation, and nausea. These effects may diminish with continued therapy or may be relieved by a reduction in dosage.

Postural Effects

Prazosin may cause syncope with sudden loss of consciousness. (See Cautions: Precautions and Contraindications.) Syncopal episodes occur unpredictably and have no relationship to plasma prazosin concentrations. The incidence of syncope is greatest in patients given an initial dose of 2 mg or more (approximately 1%) and may be minimized by administering 1 mg of the drug initially with subsequent gradual increases in dosage. Results of one study suggest that administration of prazosin with food may reduce the frequency of hypotension and dizziness in some patients. Syncope, which is self-limiting, may result from an excessive postural hypotensive effect; syncopal episodes occasionally have been preceded by tachycardia with heart rates of 120-160 beats/minute. Syncopal episodes usually have occurred within 30-90 minutes after the initial dose of prazosin and occasionally have been associated with rapid dosage increases or the introduction of another hypotensive drug to the regimen of patients taking high dosages of prazosin.

Intraoperative Floppy Iris Syndrome

A condition named intraoperative floppy iris syndrome (IFIS) has been observed during cataract surgery in some patients treated with α1-adrenergic blocking agents. IFIS is a variant of small pupil syndrome and is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with mydriatics, and potential prolapse of the iris toward the phacoemulsification incisions. Most reported cases of IFIS occurred in patients who continued α1-blocker therapy at the time of cataract surgery. Some cases were reported in patients who had discontinued such therapy prior to surgery, generally 2 to 14 days prior to surgery, but occasionally 5 weeks to 9 months prior to surgery.(See Cautions: Precautions and Contraindications.)

GI Effects

Nausea is the most common adverse GI effect of prazosin, occurring in about 5% of patients. Other adverse GI effects such as vomiting, diarrhea, constipation, and abdominal discomfort and/or pain have also been reported.

Cardiovascular Effects

Palpitation is the most common adverse cardiovascular effect of prazosin, occurring in about 5% of patients. In addition to syncope, other adverse cardiovascular effects of the drug include edema, dyspnea, orthostatic hypotension, tachycardia, and angina.(See Cautions: Postural Effects.) Nonspecific chest pain also has been reported in a patient receiving prazosin for posttraumatic stress disorder.

Nervous System Effects

Dizziness is the most common adverse effect of prazosin, occurring in about 10% of patients. Headache or drowsiness occur in about 8% of patients, and lack of energy or weakness occur in about 7% of patients. Other adverse nervous system effects of prazosin which occur rarely include nervousness, vertigo, depression, paresthesia, hallucinations, and insomnia.

Worsening of narcolepsy (e.g., exacerbation of associated cataplexy) has been associated with prazosin therapy in patients with a history of this disorder. Although the manufacturers state that a causal relationship to prazosin has not been established to date, the frequency of cataplectic attacks decreased when the drug was withdrawn and increased when it was resumed in at least 2 patients. In addition, prazosin has been shown to exacerbate canine narcolepsy-cataplexy, probably secondary to inhibition of a subtype of α1-adrenergic receptor (e.g., α1b) in the CNS. Therefore, some clinicians recommend that prazosin not be used in patients with a history of narcolepsy.

Dermatologic Effects

Adverse dermatologic effects associated with prazosin include rash, pruritus, alopecia, and lichen planus.

Other Adverse Effects

Other adverse effects reported to occur with prazosin include urinary frequency, incontinence, impotence, priapism, blurred vision, epistaxis, tinnitus, reddened sclera, dry mouth, nasal congestion, liver function test result abnormalities, pancreatitis, diaphoresis, fever, positive ANA titer, and arthralgia. A transient fall in leukocyte count and increased serum uric acid and BUN concentrations have also been reported during prazosin therapy. Single reports of pigmentary mottling and serous retinopathy, and a few cases of cataract development or disappearance have been reported, but these have not been directly attributable to the drug. In slit-lamp and funduscopic studies, no drug-related abnormal ophthalmologic findings have been reported.

Precautions and Contraindications

Because syncope and orthostatic hypotension may occur in patients receiving prazosin, careful monitoring of blood pressure during initial titration or subsequent upward adjustment in dosage is recommended in patients receiving prazosin; patients also should be monitored for possible symptoms of orthostatic hypotension. Patients receiving prazosin should be warned of the possibility of prazosin-induced postural dizziness and advised of measures to take if it develops (e.g., lying down). During initiation of prazosin therapy, the patient should be cautioned to avoid situations where injury could result if syncope occurs. If syncope occurs, the patient should be placed in the recumbent position and treated supportively as necessary. Patients who engage in potentially hazardous activities such as operating machinery or driving motor vehicles should be warned about possible drowsiness, dizziness, or lightheadedness. (See Cautions: Postural Effects.)

Intraoperative floppy iris syndrome (IFIS) has been observed during cataract surgery in some patients treated with α1-adrenergic blocking agents (see Cautions: Intraoperative Floppy Iris Syndrome). If a patient scheduled for cataract surgery has received such agents, the ophthalmologist should be prepared to modify the surgical technique (e.g., through use of iris hooks, iris dilator rings, or viscoelastic substances) to minimize complications of IFIS. There does not appear to be a benefit from discontinuing α1-blocker therapy prior to cataract surgery.

The possibility of carcinoma of the prostate and other conditions associated with manifestations that mimic those of benign prostatic hyperplasia (BPH) should be excluded in any patient for whom prazosin therapy for presumed BPH is being considered.

Patients receiving prazosin for posttraumatic stress disorder (PTSD) should be informed that prazosin may help reduce nightmares and improve their sleep and other symptoms, but that the drug does not cure PTSD and that their nightmares, anxiety, and other PTSD-related symptoms may return if the drug is stopped.

Caution should be used when adding prazosin to a preexisting antihypertensive regimen or when adding other hypotensive agents to a prazosin regimen in order to avoid a possible rapid fall in blood pressure. (See Drug Interactions: Diuretics and Hypotensive Agents.) Caution also should be used when administering prazosin to patients with chronic renal failure as they may require only small doses of the drug.

Prazosin is contraindicated in patients with known hypersensitivity to the drug, any other quinazoline derivative (e.g., alfuzosin, doxazosin, terazosin), or any ingredient in the commercially available formulation.

Pediatric Precautions

The manufacturers state that safety and efficacy of prazosin in children have not been established. (See Dosage and Administration: Dosage.)

For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients,

Mutagenicity and Carcinogenicity

No evidence of prazosin-induced mutagenicity was seen with in vivo tests.

No evidence of carcinogenesis was seen in rats receiving prazosin hydrochloride dosages more than 225 times the usual maximum recommended human dosage for 18 months.

Pregnancy, Fertility, and Lactation


Prazosin hydrochloride has been associated with decreased litter size at birth and at 1, 4, and 21 days of age in rats receiving more than 225 times the usual maximum recommended human dosage; no evidence of drug-related external, visceral, or skeletal fetal abnormalities was observed. No prazosin-related external, visceral, or skeletal abnormalities were observed in the offspring of pregnant rabbits and monkeys receiving dosages more than 225 and 12 times the usual maximum recommended human dosage, respectively. Prazosin has been used alone or in combination with other hypotensive agents for the management of severe hypertension in a limited number of pregnant women without apparent adverse effect on the fetus. There are no adequate and well-controlled studies to date using prazosin in pregnant women, however, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.


Decreased fertility has occurred in male and female rats receiving prazosin dosages of 75 mg/kg (225 times the usual maximum recommended human dosage) but did not occur in those receiving 25 mg/kg (75 times the usual maximum recommended human dosage). Testicular changes consisting of atrophy and necrosis have occurred in rats and dogs receiving prazosin dosages of 25 mg/kg daily for a year or longer but no such changes occurred in those receiving 10 mg/kg daily (30 times the usual maximum recommended human dosage). Because of the testicular changes observed in animals, a group of patients receiving long-term prazosin therapy was monitored for 17-ketosteroid excretion, but no changes indicating a drug effect were observed. In addition, a group of males receiving prazosin for up to 51 months did not exhibit changes in sperm morphology suggestive of a drug effect.


Since prazosin is distributed into milk in small amounts, the drug should be used with caution in nursing women.

Drug Interactions

Analgesics and Antipyretics

Although clinical experience is limited, prazosin has been administered concomitantly with aspirin, indomethacin, phenylbutazone (no longer commercially available in the US), or propoxyphene (no longer commercially available in the US) without any apparent adverse interaction.

Antiarrhythmic Agents

Although clinical experience to date is limited, prazosin has been administered concomitantly with procainamide, propranolol (see Drug Interactions: Diuretics and Hypotensive Agents), or quinidine without any apparent adverse drug interaction.

Antidiabetic Agents

Although clinical experience to date is limited, prazosin has been administered concomitantly with insulin, chlorpropamide, phenformin (no longer commercially available in the US), tolazamide, and tolbutamide without any apparent adverse drug interaction.

Antigout Agents

Although clinical experience is limited, prazosin has been administered concurrently with allopurinol, colchicine, or probenecid without any apparent adverse interaction.

CNS Depressants

Although clinical experience is limited, prazosin has been administered concurrently with chlordiazepoxide, diazepam, or phenobarbital without any apparent adverse interaction.


Although clinical experience is limited, prazosin has been administered concomitantly with digoxin without any apparent adverse interaction.

Diuretics and Hypotensive Agents

When prazosin is administered with diuretics or other hypotensive agents, particularly β-adrenergic blocking agents (e.g., propranolol), the hypotensive effect of prazosin may be increased. This effect is usually used to therapeutic advantage, but careful adjustment of dosage is necessary when these drugs are used concomitantly. (See Dosage and Administration: Dosage.)

Phosphodiesterase Type 5 Inhibitors

Concomitant administration of prazosin and a phosphodiesterase type 5 (PDE5) inhibitor (e.g., sildenafil, tadalafil, vardenafil) may result in additive hypotensive effects and symptomatic hypotension. Therefore, PDE5 inhibitor therapy should be initiated at the lowest possible dosage in patients receiving prazosin.(See Dosage and Administration: Dosage.)

For further information on this potential drug interaction,

Protein-bound Drugs

Since prazosin is highly bound to plasma proteins, the possibility that it may interact with other highly protein-bound drugs should be considered.



There is intraindividual and interindividual variation in the rate of absorption and plasma concentrations of prazosin. The absolute oral bioavailability of prazosin is also variable but is reported to average about 60% (range: 43-82%). Results of one study indicate that the presence of food may delay absorption of the drug in some patients, but does not affect the extent of absorption.

Following oral administration of prazosin hydrochloride, plasma concentrations of the drug reach a peak in 2-3 hours in most fasting patients. Plasma concentrations of prazosin generally do not correlate with therapeutic effect. One manufacturer reports that plasma concentrations of the drug after a single 5-mg dose range from 0.01-0.075 mcg/mL. Blood pressure begins to decrease within 2 hours after an oral dose; the maximum decrease occurs in 2-4 hours. The hypotensive effect of prazosin lasts less than 24 hours. At fixed dosage levels, 4-6 weeks of therapy are required before the full antihypertensive effect of the drug is achieved.


Animal studies indicate that prazosin is widely distributed in body tissues. After IV administration in dogs, highest concentrations of the drug are found in the lungs, coronary arteries, aorta, paw arteries and heart; the lowest concentrations are in the brain. During prazosin therapy, approximately 97% of the drug in plasma is bound to proteins. Prazosin crosses the blood-brain barrier. It is not known whether the drug crosses the placenta. Prazosin is distributed into milk in small amounts.


The plasma half-life of prazosin after oral administration has been reported to be 2-4 hours.

Animal studies show that prazosin hydrochloride is metabolized extensively in the liver, principally by demethylation and conjugation, and excreted as unchanged drug (5-11%) and metabolites. Four of the metabolites have been shown to possess 10-25% of the hypotensive activity of prazosin and they may contribute to the antihypertensive effect of the drug. Approximately 6-10% of a dose is excreted in urine and the remainder in feces via bile.

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