What is the recommended starting dose of Prazosin for hypertension?

Prazosin Dosing for Hypertension

The recommended starting dose of prazosin for hypertension is 1 mg given two to three times daily, with critical emphasis on never exceeding 1 mg for the initial dose to minimize the risk of severe first-dose hypotension and syncope. 1

Initial Dosing Protocol

• Start with 1 mg twice or three times daily as the FDA-approved initial regimen 1
• The 2 mg and 5 mg capsules are explicitly contraindicated for initial therapy 1
• Some protocols advocate an even more conservative approach of 0.5 mg on day 1, followed by 0.5 mg three times daily on days 2-4, then advancing to 1 mg three times daily 2

Critical First-Dose Phenomenon

• Syncope occurs in approximately 1% of patients given an initial dose of 2 mg or greater, typically within 30-90 minutes of the first dose 1
• This can manifest as sudden loss of consciousness, occasionally preceded by severe tachycardia (120-160 bpm) 1
• Even the recommended 0.5 mg initial dose has caused severe hypotension with consciousness disturbance in high-risk patients, particularly those with recent cerebral hemorrhage 3
• Patients should be counseled to take the first dose at bedtime and avoid situations where injury could occur if syncope develops 1

Dose Titration and Maintenance

• Increase dosage slowly after the initial period to minimize adverse effects 1
• Therapeutic dosages most commonly range from 6-15 mg daily in divided doses 1
• Maximum dose is 20 mg daily in divided doses, though some patients may benefit from up to 40 mg daily 1
• Doses above 20 mg usually do not increase efficacy 1
• After initial titration, some patients can be maintained on twice-daily dosing 1

Use in Combination Therapy

• When adding prazosin to existing antihypertensive therapy, reduce the dose to 1-2 mg three times daily and retitrate 1
• Prazosin is reserved as a second-line or add-on agent in resistant hypertension, typically after failure of ACE inhibitors/ARBs, calcium channel blockers, and thiazide diuretics 4
• It may be added as a fourth-line agent when spironolactone is not tolerated or contraindicated 4
• Hypotension may develop when prazosin is combined with beta-blockers 1

Clinical Context and Patient Selection

• Prazosin is classified as an alpha-1 blocker and is not recommended as a first-line agent for hypertension 4
• It is generally reserved as a last-line option due to significant CNS adverse effects, particularly in older adults 4
• May be considered as a second-line agent in patients with concomitant benign prostatic hyperplasia 4
• The drug is associated with orthostatic hypotension, especially in older adults 4

Monitoring Requirements

• Assess blood pressure and heart rate before each dose, particularly during initiation 5
• Monitor for orthostatic changes, especially in elderly patients 5
• Common adverse effects include dizziness and lightheadedness associated with blood pressure lowering 1

Important Contraindications and Warnings

• Avoid abrupt discontinuation when used in combination regimens 4
• Concomitant administration with PDE-5 inhibitors can result in additive blood pressure lowering and symptomatic hypotension; PDE-5 inhibitor therapy should be initiated at the lowest dose 1
• Prolonged erections and priapism have been reported; seek immediate medical assistance for erections lasting longer than 4 hours 1