What is the recommended dosing for prazosin in an adult patient with hypertension or benign prostatic hyperplasia and no significant cardiovascular history?

Prazosin Dosing

For hypertension, start prazosin at 1 mg two to three times daily (taken at bedtime initially to minimize first-dose syncope), then titrate slowly to a maintenance dose of 6-15 mg daily in divided doses, with a maximum of 40 mg daily if needed. 1

Hypertension Dosing Protocol

Initial Dosing

• Start with 1 mg at bedtime to reduce the risk of first-dose syncope, which occurs in approximately 0.15% of patients (1 in 667) 2
• After the first dose is tolerated, advance to 1 mg two to three times daily 1
• Prazosin requires 2-3 times daily dosing for adequate 24-hour blood pressure control—once-daily dosing is insufficient 3, 4

Titration and Maintenance

• Slowly increase the dose based on blood pressure response 1
• Therapeutic range: 6-15 mg daily in divided doses (most commonly used and effective) 1
• Maximum dose: 20 mg daily for most patients; doses above 20 mg rarely increase efficacy 1
• A few patients may benefit from up to 40 mg daily in divided doses 1
• After initial titration, some patients can be maintained on twice-daily dosing 1

Important Considerations for Hypertension

• Prazosin is a second-line agent for hypertension, not first-line therapy 3
• Alpha-1 blockers like prazosin are associated with orthostatic hypotension, especially in older adults 3
• They may be considered as second-line agents in patients with concomitant benign prostatic hyperplasia (BPH) 3
• When adding other antihypertensive agents, reduce prazosin to 1-2 mg three times daily and retitrate 1

Benign Prostatic Hyperplasia (BPH)

Do not prescribe prazosin for BPH—the American Urological Association guidelines explicitly state that data are insufficient to support prazosin use for BPH 5, 4. Instead, use terazosin, doxazosin, tamsulosin, or alfuzosin, which have established efficacy with 4-6 point improvements in AUA Symptom Index 5, 4.

While older research from 1990-1992 suggested prazosin might be effective for BPH at doses of 1-9 mg daily 6, 7, the lack of rigorous clinical trial data compared to other alpha-blockers is the specific reason prazosin is excluded from current BPH treatment recommendations 5, 4.

PTSD-Associated Nightmares

For PTSD-related nightmares, prazosin has Level A evidence and is recommended as first-line therapy 3, 4.

Dosing Protocol for Nightmares

• Start with 1 mg at bedtime 3, 4
• Increase by 1-2 mg every few days until an effective dose is reached 3, 4
• Average effective dose: approximately 3 mg (range 1-10+ mg) 3, 4
• Higher doses (mean 9.5-13.3 mg/day) have been used in some trials for severe PTSD-associated nightmares 3, 4
• Veterans with chronic PTSD may require mean doses of 13 ± 3 mg/day 3
• Active-duty soldiers may require mean bedtime doses of 15.6 ± 6.0 mg for men and 7.0 ± 3.5 mg for women 3

Critical Safety Monitoring

Orthostatic Hypotension Risk

• Elderly patients and those on multiple medications face the highest risk for orthostatic hypotension and falls 5, 4
• Monitor blood pressure closely, especially after initiation or dose changes 4
• First-dose syncope risk mandates initial dosing at bedtime for all indications 5, 1

Drug Interactions

• Combining prazosin with PDE-5 inhibitors (sildenafil, tadalafil, etc.) causes additive blood pressure lowering and symptomatic hypotension; initiate PDE-5 inhibitors at the lowest dose in patients taking prazosin 1
• Combining with other CNS depressants may cause additive sedation and orthostatic hypotension 4

Discontinuation

• Avoid abrupt discontinuation, though prazosin does not cause withdrawal phenomena like clonidine 5, 4
• Be especially cautious in elderly patients who are more susceptible to falls from orthostatic hypotension 4

Common Pitfalls to Avoid

• Do not use once-daily dosing for hypertension—prazosin requires 2-3 times daily administration for adequate 24-hour blood pressure control 3, 4
• Do not prescribe prazosin for BPH—guidelines are explicit that evidence is insufficient; use terazosin, doxazosin, tamsulosin, or alfuzosin instead 5, 4
• Do not start with doses higher than 1 mg—this significantly increases first-dose syncope risk 1, 2
• Do not forget to check orthostatic vital signs in elderly patients and those on multiple medications 4