What is the starting dose threshold for prazosin in a patient with a risk of orthostatic hypotension?

Prazosin Starting Dose in Patients at Risk for Orthostatic Hypotension

Start prazosin at 1 mg at bedtime in all patients at risk for orthostatic hypotension, never exceeding this initial dose. 1, 2

Initial Dosing Protocol

• The FDA-approved starting dose is 1 mg administered at bedtime, which is the absolute maximum initial dose for any patient 2
• The American Academy of Sleep Medicine recommends starting at 1 mg at bedtime and increasing by 1-2 mg every few days until reaching an effective dose 1
• Patients should always be started on 1 mg capsules—the 2 mg and 5 mg capsules are explicitly not indicated for initial therapy 2

Critical Safety Considerations

• The incidence of syncope is approximately 1% when initial doses of 2 mg or greater are used, which is why the 1 mg threshold must never be exceeded initially 2
• Syncopal episodes typically occur within 30-90 minutes of the first dose and are believed to result from excessive postural hypotension 2
• The FDA warns that even at recommended doses, prazosin can cause syncope with sudden loss of consciousness, particularly in patients with pre-existing orthostatic hypotension risk 2

High-Risk Patient Populations Requiring Extra Caution

• Elderly patients are at substantially higher risk for prazosin-induced hypotension and should be monitored closely 1, 3
• Patients on concurrent antihypertensive medications face increased risk and may require even more conservative dosing 1
• The European Society of Cardiology recommends avoiding alpha-blockers like prazosin in elderly/frail patients with orthostatic hypotension unless compelling indications exist 3
• Patients with standing systolic BP <110 mmHg should not receive prazosin 3

Pre-Treatment Assessment

• Measure orthostatic blood pressure before initiating prazosin: have the patient sit or lie for 5 minutes, then measure BP at 1 and 3 minutes after standing 3
• If orthostatic hypotension is already present (standing systolic BP <110 mmHg), prazosin is contraindicated 3
• Consider withholding diuretics for 1 day before initiating prazosin therapy to minimize first-dose hypotension 4

Dose Titration Strategy

• After the initial 1 mg bedtime dose is tolerated, increase by 1-2 mg every few days as needed 1
• Monitor blood pressure after each significant dose increase, specifically assessing for orthostatic changes 1, 5
• The therapeutic dosage range is typically 6-15 mg daily in divided doses, though some patients require up to 20-40 mg daily 2

When Adding Prazosin to Existing Antihypertensive Therapy

• When adding prazosin to a patient already on other antihypertensives, reduce prazosin dose to 1-2 mg three times daily and retitrate carefully 2
• This is particularly important because concomitant administration with other blood pressure-lowering agents (including PDE-5 inhibitors) can result in additive hypotensive effects 2

Common Pitfall to Avoid

• Never start with doses higher than 1 mg, even if the patient "seems stable"—clinical trials demonstrate that syncope risk increases substantially with initial doses ≥2 mg 2, 4
• Do not assume that because a patient tolerates other antihypertensives well, they will tolerate higher initial prazosin doses—the first-dose phenomenon is unique to alpha-blockers 2, 6
• Even the recommended 0.5-1 mg starting dose can cause severe hypotension in patients with recent stroke, so extreme caution is warranted in this population 6