Prazosin hydrochloride is an α1-adrenergic blocking agent.
Prazosin hydrochloride is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. However, because of established clinical benefits (e.g., reductions in overall mortality and in adverse cardiovascular, cerebrovascular, and renal outcomes), current evidence-based practice guidelines for the management of hypertension in adults generally recommend the use of drugs from 4 classes of antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics).501, 502, 503, 504, 1200, 1213
In a randomized, double-blind clinical study (the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]),167, 173, 174 doxazosin, an α1-blocker, was less effective in lowering mean systolic blood pressure (by about 2-3 mm Hg) than chlorthalidone, a thiazide-like diuretic.167 In order to achieve target blood pressure in hypertensive patients, use of doxazosin required additional hypotensive therapy more frequently than chlorthalidone.167 In addition, interim analysis (median follow-up: 3.3 years) of this study indicated 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 a higher incidence of combined cardiovascular disease events (including twice the risk of congestive heart failure than use of chlorthalidone.167, 168 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.167, 168 Therefore, based on these findings, the trial's Data Safety and Monitoring Board recommended that the α-blocker treatment arm be terminated prematurely.167, 168, 174 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.173, 174, 175
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.230, 501, 502, 504, 1200 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.502, 504, 1200 Therapy with an α1-blocker is most effective when used in combination with a diuretic.504 Some experts state that an α1-blocker may be a second-line agent in antihypertensive treatment regimens in men with coexisting benign prostatic hyperplasia (BPH);504, 1200 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.230
The beneficial effects of α1-blockers on blood glucose and lipid concentrations may mitigate some of the adverse metabolic effects of diuretics,504 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).153, 161 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.153, 161, 1200 Blood pressure response to α1-blockers appears to be comparable in white and black patients.153, 161
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, see Uses: Hypertension in Adults, in the Thiazides General Statement 40:28.20.
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.112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 176 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,112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133 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.112, 125, 127, 129, 133, 150
Therapy with α1-blockers appears to be less effective in relieving irritative than obstructive symptomatology.147, 148 In addition, therapy with the drugs generally can be expected to produce less subjective and objective improvement than prostatectomy,119, 124, 133 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).121, 125, 129, 131, 133, 135, 150, 152 While symptomatic improvement has been observed in the short term in some patients receiving prazosin therapy,114, 118, 120, 123 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.125, 129, 196 Currently available α1-adrenergic blockers (with the exception of prazosin, for which there are insufficient data to compare) are considered comparably effective.176
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;112, 113, 114, 115, 116, 117, 122, 125, 128, 132 alleviation of both obstructive and irritative manifestations of the hyperplasia has been reported in some patients with prazosin therapy.114, 118, 139, 145 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.112, 118, 119, 120, 123, 124, 126, 127, 129
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.176
For additional information on the use of α1-blockers in the management of BPH, see Uses: Benign Prostatic Hyperplasia, in Doxazosin 24:20.
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).200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 215, 216, 217, 222, 225 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.200, 201, 202
Although selective serotonin-reuptake inhibitors (SSRIs; e.g., paroxetine, sertraline) generally have been considered the drugs of choice for the pharmacologic treatment of PTSD,200, 212, 213, 214, 215, 217, 222, 225 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.200, 207, 210, 217 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.200, 214, 225
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.200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 215, 216, 217 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).206, 207, 209, 210, 211
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.203, 204 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.203 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).203 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.204 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).204
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.205 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.217 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).217 Prazosin therapy was generally found to be well tolerated when used in the treatment of PTSD-associated nightmares and other symptoms.200, 202, 203, 204, 207, 209, 210, 211, 217, 220
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.201, 204, 212, 215, 217, 220, 222, 225 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.206 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.200, 201, 202, 203, 204, 205, 206, 207, 208, 212, 215, 216, 225 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.200, 201, 203, 204, 208, 216 Several controlled studies, including comparative and augmentation trials, are planned or currently underway to further evaluate prazosin in patients with this disorder.200, 202, 216
For additional information on management of PTSD, see Uses: Posttraumatic Stress Disorder, in Paroxetine 28:16.04.20.
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†102, 103, 104 and ergotamine-induced peripheral ischemia†.105
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.
For the management of hypertension in adults, the usual initial 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 in divided doses.101 The manufacturer states that the usual maintenance dosage is 6-15 mg daily given in divided doses.101 For maintenance therapy, prazosin may be administered twice daily in some patients. Some experts state that the usual dosage range is 2-20 mg daily, administered in 2 or 3 divided doses.1200
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 have recommended an 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.195 (See Cautions: Pediatric Precautions.) For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
Blood Pressure Monitoring and Treatment Goals
Blood pressure should be monitored regularly (i.e., monthly) during therapy and dosage of the antihypertensive drug adjusted until blood pressure is controlled.1200 If an adequate blood pressure response is not achieved, the dosage may be increased or another antihypertensive agent with demonstrated benefit and preferably with a complementary mechanism of action (e.g., angiotensin-converting enzyme [ACE] inhibitor, angiotensin II receptor antagonist, calcium-channel blocker, thiazide diuretic) may be added; if target blood pressure is still not achieved with the use of 2 antihypertensive agents, a third drug may be added.1200, 1216 (See Uses: Hypertension.) In patients who develop unacceptable adverse effects with prazosin, the drug should be discontinued and another antihypertensive agent from a different pharmacologic class should be initiated.1216
The goal of hypertension management and prevention is to achieve and maintain optimal control of blood pressure.1200 However, the optimum blood pressure threshold for initiating antihypertensive drug therapy and specific treatment goals remain controversial.505, 506, 507, 508, 515, 523, 530, 1201, 1207, 1209, 1222 A 2017 multidisciplinary hypertension guideline from the American College of Cardiology (ACC), American Heart Association (AHA), and a number of other professional organizations generally recommends a blood pressure goal of less than 130/80 mm Hg in all adults, regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200, 1207 Many patients will require at least 2 drugs from different pharmacologic classes to achieve this blood pressure goal; the potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs also should be considered when deciding a patient's blood pressure treatment goal.1200, 1220
For additional information on target levels of blood pressure and on monitoring therapy in the management of hypertension, see Blood Pressure Monitoring and Treatment Goals under Dosage: Hypertension, in Dosage and Administration in the Thiazides General Statement 40:28.20.
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.112, 118, 119, 120, 123, 124, 126, 127, 129
The optimum dosage regimen of prazosin for the management of posttraumatic stress disorder (PTSD)† in adults has not been fully established.200, 201, 212 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.200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 217, 220 Some clinicians recommend monitoring patients receiving prazosin for PTSD for first-dose syncope and orthostatic hypotension, particularly early in therapy.200, 220, 224 (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.200, 203, 206, 210, 212, 217, 220 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.222, 224, 225 Although prazosin usually has been given once daily at bedtime, particularly when lower daily dosages have been used,200, 225 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.200 Symptom relief appears to occur within several days to 2 weeks after beginning therapy with the drug.201, 209
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).201, 212, 213, 222, 225 Some PTSD patients have received the drug for up to 6 years.217 Because a rapid return of symptoms following prazosin discontinuance has been reported,201, 203, 207, 209, 210 some patients may require therapy indefinitely.225
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.
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.101 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.101
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.101, 218 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.101, 218 Most reported cases of IFIS occurred in patients who continued α1-blocker therapy at the time of cataract surgery.218 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.218 (See Cautions: Precautions and Contraindications.)
Nausea is the most common adverse GI effect of prazosin, occurring in about 5% of patients.101 Other adverse GI effects such as vomiting, diarrhea, constipation, and abdominal discomfort and/or pain have also been reported.
Palpitation is the most common adverse cardiovascular effect of prazosin, occurring in about 5% of patients.101 In addition to syncope, other adverse cardiovascular effects of the drug include edema, dyspnea, orthostatic hypotension, tachycardia, and angina.101 (See Cautions: Postural Effects.) Nonspecific chest pain also has been reported in a patient receiving prazosin for posttraumatic stress disorder.223
Dizziness is the most common adverse effect of prazosin, occurring in about 10% of patients.101 Headache or drowsiness occur in about 8% of patients, and lack of energy or weakness occur in about 7% of patients.101 Other adverse nervous system effects of prazosin which occur rarely include nervousness, vertigo, depression, paresthesia, hallucinations, and insomnia.
Worsening of narcolepsy101, 107, 108 (e.g., exacerbation of associated cataplexy)107, 108 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,101 the frequency of cataplectic attacks decreased when the drug was withdrawn and increased when it was resumed in at least 2 patients.107 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)109 in the CNS.107, 108, 109, 110, 111 Therefore, some clinicians recommend that prazosin not be used in patients with a history of narcolepsy.107
Adverse dermatologic effects associated with prazosin include rash, pruritus, alopecia, and lichen planus.
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.161, 220 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).101, 218 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.101, 218 There does not appear to be a benefit from discontinuing α1-blocker therapy prior to cataract surgery.101, 218
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.155, 156
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.201, 219
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.101
The manufacturers state that safety and efficacy of prazosin in children have not been established. (See Dosage and Administration: Dosage.) Some experts state that use of centrally acting antihypertensive agents (e.g., prazosin) should be reserved for children who are not responsive to 2 or more of the preferred classes of antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, or thiazide diuretics).1150, 1230
For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
Mutagenicity and Carcinogenicity
No evidence of prazosin-induced mutagenicity was seen with in vivo tests.101
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.101
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 dosa no evidence of drug-related external, visceral, or skeletal fetal abnormalities was observed.101 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.101 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.101 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.101
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).101 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).101 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.101 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.101
Since prazosin is distributed into milk in small amounts, the drug should be used with caution in nursing women.101
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.101
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.101
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.101
Although clinical experience is limited, prazosin has been administered concurrently with allopurinol, colchicine, or probenecid without any apparent adverse interaction.101
Although clinical experience is limited, prazosin has been administered concurrently with chlordiazepoxide, diazepam, or phenobarbital without any apparent adverse interaction.101
Although clinical experience is limited, prazosin has been administered concomitantly with digoxin without any apparent adverse interaction.101
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.101 Therefore, PDE5 inhibitor therapy should be initiated at the lowest possible dosage in patients receiving prazosin.101 (See Dosage and Administration: Dosage.)
For further information on this potential drug interaction, see Drug Interactions: Antihypertensive and Hypotensive Agents, in Sildenafil 24:12.12.
Since prazosin is highly bound to plasma proteins, the possibility that it may interact with other highly protein-bound drugs should be considered.
The manufacturers state that ingestion of at least 50 mg of prazosin by a 2-year-old child produced profound drowsiness and depressed reflexes. There was no decrease in blood pressure and recovery was uneventful. A 19-year-old man who ingested approximately 200 mg of prazosin had normal CNS responses and slightly decreased blood pressure. Treatment of overdosage consisted of induction of emesis and maintaining the patient in a supine position with the head of the bed lowered; recovery was uneventful.
If overdosage of prazosin causes hypotension, supportive therapy should be initiated. The patient should be kept in the supine position; if necessary, shock may be treated with plasma volume expanders and vasopressor drugs. Renal function should be monitored. The manufacturers state that laboratory data indicate prazosin is not dialyzable because it is highly protein bound.
Prazosin reduces peripheral vascular resistance and blood pressure as a result of its vasodilating effects; the drug produces both arterial and venous dilation. Prazosin's effects appear to result principally from its selective, competitive inhibition of α1-adrenergic receptors. Prazosin's effects were initially attributed to a direct effect on vascular smooth muscle, inhibition of phosphodiesterase, and/or inhibition of dopamine β-hydroxylase with a resultant reduction in neurotransmitter synthesis; however, it is unlikely that concentrations of the drug necessary for these effects are achieved when prazosin is administered in therapeutic doses. Animal studies indicate that prazosin does not have its antihypertensive effect in the CNS. Prazosin does not interfere with nerve impulse transmission across sympathetic ganglia nor does it cause adrenergic neuronal blockade.
Prazosin reduces blood pressure in both supine and standing patients; the effect is most pronounced on diastolic blood pressure. The drug may cause postural hypotension. (See Cautions: Postural Effects.) Tolerance to the hypotensive effect has not been observed during long-term prazosin therapy in hypertensive patients. Prazosin generally causes no change in heart rate or cardiac output in the supine position. Cardiovascular responses to exercise (e.g., increased heart rate and cardiac output) are maintained during prazosin therapy. Reports on the effect of the drug on glomerular filtration rate and renal plasma flow indicate that these parameters may increase or show no marked change. In patients with chronic renal failure, prazosin produces no clinically important change in renal function. In a limited number of patients treated with prazosin, plasma renin activity (PRA) decreased; however, no appreciable effect on PRA was demonstrated in other patients.
In patients with congestive heart failure, prazosin markedly decreases systemic and pulmonary venous pressures and right atrial pressure, and increases cardiac output. Systemic blood pressure and systemic vascular resistance are moderately decreased in these patients; pulmonary vascular resistance is decreased and heart rate may be slightly decreased or unchanged. In patients with congestive heart failure precipitated or exacerbated by mitral or aortic regurgitation, prazosin may increase cardiac output and decrease regurgitant volume.
The precise mechanism of action of prazosin in posttraumatic stress disorder (PTSD) has not been fully elucidated; however, preliminary studies suggest that norepinephrine and α1-adrenergic receptors play an important role in the pathophysiology of PTSD-associated nightmares, arousal, selective attention, and vigilance.200, 201, 203, 204, 205, 206, 207, 208, 209, 210, 216, 217, 220 Norepinephrine concentrations in the cerebrospinal fluid appear to correlate with PTSD symptom severity.201, 217, 220 Hyperresponsiveness of postsynaptic α1-adrenergic receptors occurs primarily at night and can disrupt certain stages of the sleep cycle (stage 1, stage 2, rapid eye movement [REM]) in which PTSD-associated nightmares are known to occur.200, 201, 203, 204, 205, 208, 210, 216, 217 In preclinical and clinical studies, prazosin has been shown to reduce the effects of α1-adrenergic receptor hyperstimulation and to help normalize the sleep cycle.200, 203, 205, 206, 211, 220 In a placebo-controlled trial of prazosin in civilian trauma-related PTSD, prazosin increased total sleep time, REM sleep time, and mean REM period duration compared with placebo without producing a sedative-like effect on sleep onset latency.205
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.200, 204, 205, 206, 208, 210 It is not known whether the drug crosses the placenta. Prazosin is distributed into milk in small amounts.101
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.
Prazosin hydrochloride is a quinazoline-derivative postsynaptic α1-adrenergic blocking agent. The drug is chemically and pharmacologically related to alfuzosin, doxazosin, and terazosin. Prazosin hydrochloride occurs as a white to tan powder, is slightly soluble in water and very slightly soluble in alcohol, and has a pKa of 6.5 in 1:1 water and ethanol solution.
Prazosin hydrochloride capsules should be stored in well-closed, light-resistant containers at 20-25°C.221
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 1 mg (of prazosin)* | ||
2 mg (of prazosin)* | Minipress® | Pfizer | ||
Prazosin Hydrochloride Capsules | ||||
5 mg (of prazosin)* | Minipress® | Pfizer | ||
Prazosin Hydrochloride Capsules |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
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