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Prazosin (Monograph)

Brand name: Minipress
Drug class: Sclerosing Agents
VA class: CV150
CAS number: 19237-84-4

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Postsynaptic α1-adrenergic blocking agent; quinazoline derivative.101 b

Uses for Prazosin

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).101 1200

Not considered a preferred agent for initial management of hypertension according to current evidence-based hypertension guidelines, but may be useful in the management of resistant hypertension as a component of combination therapy.501 502 503 504 1200

Most effective when used in combination with a diuretic; beneficial effects of α1-blockers on blood glucose and lipid concentrations also may mitigate some adverse metabolic effects of diuretics.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 however, 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

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210

Other hypertension guidelines generally have based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk, and have used higher BP thresholds and target BPs in elderly patients501 504 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.1200 1220 1229

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.1200

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.1200

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200 Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.502 1200

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200

Benign Prostatic Hyperplasia

Has been used to reduce urinary obstruction and relieve associated manifestations in patients with symptomatic BPH† [off-label]; efficacy relative to other α1-adrenergic blockers remains to be established.112 113 114 115 116 117 118 119 120 122 123 124 125 126 127 128 129 130 131 132 133

Posttraumatic Stress Disorder (PTSD)

Has been used in the management of PTSD† [off-label], particularly in combat veterans and in patients experiencing nighttime PTSD symptoms (e.g., nightmares, sleep disturbances).200 201 202 203 204 205 206 207 208 209 210 211 212 215 216 217 221 222 225

Some clinicians recommend prazosin as first-line or alternative therapy when treating PTSD patients with prominent nighttime symptoms, particularly in combat veterans.201 204 212 215 217 222 225 Further studies necessary in civilians with noncombat trauma-related PTSD and in treatment of daytime PTSD symptoms.200 201 203 204 208 216

Prazosin Dosage and Administration

General

BP Monitoring and Treatment Goals

Administration

Oral Administration

Administer orally in divided doses 2 or 3 times daily.101

Manufacturers make no specific recommendations regarding administration with meals.101 221

Dosage

Available as prazosin hydrochloride; dosage expressed in terms of prazosin.101 b

Individualize dosage according to patient response and tolerance.101 b Initiate at low dosage to minimize frequency of postural hypotension and syncope.101 b

Postural effects are most likely to occur 2–6 hours after a dose; monitor BP during this period after first dose and with any dosage increases.161

If therapy is interrupted for a few days, restart using initial dosage regimen.

Pediatric Patients

Hypertension† [off-label]
Oral

Some experts have recommended an initial dosage of 0.05–0.1 mg/kg daily given in 3 divided doses.195 Increase dosage as necessary up to a maximum of 0.5 mg/kg daily given in 3 divided doses.195 (See Pediatric Use under Cautions.)

Adults

Hypertension
Oral

Initially, 1 mg 2 or 3 times daily.101 b Do not initiate with higher dosages.101 b May increase dosage gradually to 20 mg daily given in divided doses.101 b

Usual maintenance dosage: Manufacturer states 6–15 mg daily given in divided doses.101 b Some experts state 2–20 mg daily, administered in 2 or 3 divided doses.1200

When other hypotensive agents or diuretics are added to existing prazosin therapy, reduce dosage to 1 or 2 mg 3 times daily; gradually increase according to patient's response and tolerance.101 b

Posttraumatic Stress Disorder† [off-label]
Oral

Optimum dosage not established.200 201 212 In clinical studies, usual initial dosage was 1 mg at bedtime; dosage was then gradually increased based on patient's response and tolerance.200 201 202 203 204 205 206 207 208 209 210 211 212 217 220 Maintenance dosages of 1–25 mg daily (given once daily at bedtime or in 2 divided doses) have been used.200 203 206 210 212 217 220 225 Some experts recommend a target maintenance dosage of 1–10 mg daily; others recommend a higher target dosage of 2–20 mg daily.224 225

Prescribing Limits

Pediatric Patients

Hypertension† [off-label]
Oral

Maximum 0.5 mg/kg daily.195

Adults

Hypertension
Oral

Maximum 20 mg daily.101 b Although higher dosages usually do not increase efficacy, a few patients may benefit from ≤40 mg daily.101 b

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.b

Renal Impairment

Initially, 1 mg twice daily.b Patients with chronic renal failure may require only small dosages.b

Geriatric Patients

No specific dosage recommendations at this time;b generally increase dosage more slowly in geriatric hypertensive patients than in younger adults.153

Detailed Prazosin dosage information

Cautions for Prazosin

Contraindications

Known hypersensitivity to prazosin, quinazolines (e.g., alfuzosin, doxazosin, terazosin), or any ingredient in the formulation.101

Warnings/Precautions

Warnings

Postural Hypotension

Like other α-adrenergic blocking agents, marked hypotension, especially in the upright position, can occur; may be accompanied by syncope, palpitations, and other postural effects (e.g., dizziness, lightheadedness, vertigo).101

Postural effects are most common after an initial dose, shortly after dosing (e.g., within 90 minutes), when dosage is rapidly increased, or when other antihypertensive agents are added to therapy.101 b

To decrease risk of excessive hypotension and syncope, initiate therapy at a low dosage (i.e., 1 mg) and titrate slowly; initiate concomitant antihypertensive agents with caution.101 b

If syncope or hypotension occurs, place patient in a recumbent position and institute supportive therapy as necessary.101 b

General Precautions

Intraoperative Floppy Iris Syndrome (IFIS)

IFIS observed during cataract surgery in some patients currently receiving or previously treated with α1-adrenergic blocking agents.101 218

If patient has received α1-blockers, ophthalmologist should be prepared to modify the surgical technique (e.g., through use of iris hooks, iris dilator rings, viscoelastic substances) to minimize complications of IFIS.101 218

Benefit of discontinuing α1-blockers, including prazosin, prior to cataract surgery not established.101 218

Prostate Cancer

Exclude possibility of prostate cancer before initiation of therapy for BPH.155 156

Specific Populations

Pregnancy

Category C.101

Lactation

Distributed into milk in small amounts.101 Caution if used in nursing women.101 b

Pediatric Use

Manufacturer states that safety and efficacy not established in children.101 b

Some experts suggest reserving use of centrally acting antihypertensive agents (e.g., prazosin) for children who do not respond to therapy with 2 or more preferred classes of antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, long-acting calcium-channel blockers, or thiazide diuretics).1150 1230

Geriatric Use

Geriatric patients may be particularly susceptible to postural effects and other adverse effects.153 161

Common Adverse Effects

Dizziness, lightheadedness, headache, drowsiness, lack of energy, weakness, palpitation, nausea.101 b

Drug Interactions

Protein-bound Drugs

Potential pharmacokinetic interaction (displacement of prazosin or other protein-bound drug).b

Specific Drugs and Laboratory Tests

Drug

Interaction

Comments

Analgesic agents (aspirin, indomethacin)

No interaction observed101

Antiarrhythmic agents (procainamide, quinidine)

No interaction observed101

Antigout agents (allopurinol, colchicine, probenecid)

No interaction observed101

Antihypertensive agents (e.g., propranolol)

Possible additive hypotensive effects and symptomatic hypotension101

Initiate additional antihypertensive agents with caution; may reduce prazosin dosage and gradually increase dosage based on clinical response101

Benzodiazepines (chlordiazepoxide, diazepam)

No interaction observed101

Digoxin

No interaction observed101

Diuretics

Possible additive hypotensive effects and symptomatic hypotension101 b

Effect usually used to therapeutic advantageb

Initiate diuretics with caution; may reduce prazosin dosage and gradually increase dosage based on clinical response101

Hypoglycemic agents (insulin, chlorpropamide, phenformin [no longer commercially available in the US], tolazamide, tolbutamide)

No interaction observed101

Phenobarbital

No interaction observed101

Phosphodiesterase (PDE) type 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)

Possible additive hypotensive effects and symptomatic hypotension101

Initiate PDE type 5 inhibitor at lowest possible dosage101

Test for pheochromocytoma

Possible increase in urinary metabolite of norepinephrine and VMA; false positive results may occur in pheochromocytoma screening tests101

If elevated VMA is observed, discontinue prazosin and repeat test after 1 month101
Prazosin drug interactions (more detail)

Prazosin Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations attained within about 2–3 hours.b

Bioavailability is approximately 60%.b

Onset

In patients with hypertension, maximum reduction in BP usually occurs 2–4 hours after administration.b

Food

Food does not affect the extent of absorption; however, absorption may be delayed.b

Distribution

Extent

Not known whether prazosin crosses the placenta;b distributed into milk in small amounts.b Crosses the blood-brain barrier.200 204 205 206 208 210

Plasma Protein Binding

Approximately 97%.b

Elimination

Metabolism

Extensively metabolized, principally in the liver by demethylation and conjugation.101 b

Elimination Route

Excreted principally in feces via biliary excretion and to a lesser extent in urine (6–10%).101 b

Half-life

2–4 hours.b

Stability

Storage

Oral

Capsules

20-25°C; protect from moisture and light.221

Actions

Advice to Patients

Preparations

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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Prazosin Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

1 mg (of prazosin)*

Minipress

Pfizer

Prazosin Hydrochloride Capsules

2 mg (of prazosin)*

Minipress

Pfizer

Prazosin Hydrochloride Capsules

5 mg (of prazosin)*

Minipress

Pfizer

Prazosin Hydrochloride Capsules

AHFS DI Essentials™. © Copyright 2024, Selected Revisions April 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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