What is the recommended dosing for Prazosin (alpha-blocker) in treating hypertension and benign prostatic hyperplasia?

Prazosin Dosing

For hypertension, start prazosin at 1 mg at bedtime to minimize first-dose syncope, then titrate to 1 mg two to three times daily, with maintenance doses typically ranging from 6-15 mg daily in divided doses (maximum 40 mg/day); however, prazosin should NOT be used for benign prostatic hyperplasia as guidelines explicitly state insufficient data supports its use—choose doxazosin, terazosin, tamsulosin, or alfuzosin instead. 1, 2

Hypertension Dosing Protocol

Initial Dosing Strategy

• Start with 1 mg at bedtime to reduce the risk of first-dose syncope, a critical safety measure given that syncope occurs in approximately 0.15% of patients (1 in 667) even with proper precautions 2, 3
• After the first bedtime dose, advance to 1 mg two to three times daily 2
• The bedtime-first approach is essential because prazosin requires 2-3 times daily administration for adequate 24-hour blood pressure control, unlike doxazosin which offers once-daily dosing 1, 4

Titration and Maintenance

• Slowly increase to a total daily dose of 6-15 mg given in divided doses, which represents the most commonly employed therapeutic range 2
• Doses up to 20 mg daily generally do not increase efficacy, though some patients may benefit from increases up to 40 mg daily in divided doses 2
• After initial titration, some patients can be maintained on twice-daily dosing 2
• Mean effective doses in clinical studies average around 7 mg daily 5

Combination Therapy Considerations

• When adding a diuretic or other antihypertensive agent, reduce prazosin to 1-2 mg three times daily and retitrate 2
• If combining with PDE-5 inhibitors, initiate the PDE-5 inhibitor at the lowest dose due to additive blood pressure lowering effects and risk of symptomatic hypotension 2
• Withholding diuretics for 1 day before initiating prazosin therapy helps eliminate initial adverse effects 3

Why Prazosin Should NOT Be Used for BPH

Guideline-Based Contraindication

• The American Urological Association explicitly states that data are insufficient to support prazosin use for benign prostatic hyperplasia 1, 4
• The lack of rigorous clinical trial data compared to other alpha-blockers is the specific reason prazosin is not recommended for BPH 1, 4

Recommended Alternatives for BPH

• Use alfuzosin, doxazosin, tamsulosin, or terazosin instead, which have established efficacy producing 4-6 point improvements in AUA Symptom Index 6, 1, 4
• These agents have been extensively investigated and demonstrate consistent efficacy in partially relieving symptoms 6
• For patients with concomitant hypertension and BPH, doxazosin may be considered as it addresses both conditions, though it requires once-daily dosing of 1-16 mg/day 4

Important Caveat About Dual Diagnosis

• In men with hypertension and cardiac risk factors, doxazosin monotherapy was associated with higher incidence of congestive heart failure than other antihypertensive agents 6
• Alpha blocker use for LUTS should not be assumed to constitute optimal management of concomitant hypertension—these patients may require separate hypertension management 6

Critical Safety Monitoring

High-Risk Populations

• Elderly patients and those on multiple medications are at highest risk for orthostatic hypotension, requiring close blood pressure monitoring especially after initiation or dose changes 1
• Patients with impaired renal function can safely use prazosin, with studies showing stable or improved renal function in most cases 5

Drug Interactions and Precautions

• Avoid combining prazosin with other CNS depressants without caution, as this may cause additive sedation and orthostatic hypotension 1, 4
• Avoid abrupt discontinuation, though prazosin does not cause withdrawal phenomena like clonidine 1, 4
• Be particularly cautious in elderly patients who are more susceptible to falls from orthostatic hypotension 1

Common Side Effects

• Dizziness (most frequent, occurring in approximately 26% of patients with renal impairment), orthostatic hypotension, tiredness, and nasal congestion are the primary adverse events 5
• Sexual dysfunction is uncommon with prazosin compared to other antihypertensive agents 3
• Fluid retention is rare and less pronounced than with other antihypertensive agents, but may necessitate adding a diuretic during long-term therapy 3

Alternative Indication: PTSD-Associated Nightmares

While not the focus of this hypertension/BPH question, prazosin has Level A evidence for PTSD-associated nightmares, starting at 1 mg at bedtime and titrating by 1-2 mg every few days to an average effective dose of approximately 3 mg (range up to 9.5-13.3 mg/day in severe cases) 1, 4