Prazosin Side Effects
The most critical side effect of prazosin is orthostatic hypotension with potential syncope, particularly after the first dose, which occurs in approximately 1% of patients when initial dosing exceeds 1 mg. 1
Cardiovascular Side Effects
First-Dose Phenomenon (Most Important)
- Syncope with sudden loss of consciousness occurs within 30-90 minutes of the initial dose, believed to be due to excessive postural hypotensive effect, sometimes preceded by severe tachycardia (120-160 beats per minute). 1
- The incidence of syncope is approximately 1% when initial doses of 2 mg or greater are used, but drops to 0.15% (1 in 667 patients) when properly initiated at 1 mg. 1, 2
- Orthostatic hypotension is the most frequently reported adverse event requiring monitoring, particularly in patients with baseline low blood pressure or high fall risk. 3
Other Cardiovascular Effects
- Dizziness and lightheadedness are more common than syncope and are associated with blood pressure lowering. 1
- Reflex tachycardia can occur, though prazosin causes less reflex tachycardia than non-selective alpha blockers for similar blood pressure reductions. 4
- Standing systolic blood pressure decreases are dose-dependent, with significant reductions at 12 mg daily compared to lower doses. 5
Neurological Side Effects
- Headache is one of the most common adverse experiences reported. 6
- Fatigue occurs commonly and is typically mild-to-moderate in severity. 6
Urological Side Effects
- Priapism and prolonged erections have been reported in post-marketing experience; erections persisting longer than 4 hours require immediate medical assistance to prevent permanent penile tissue damage and loss of potency. 1
Metabolic and Fluid Effects
- Fluid retention may develop on long-term therapy, though it is rare and less pronounced than with other antihypertensive agents, potentially necessitating diuretic addition. 2
Sexual Function
- Sexual dysfunction is uncommon with prazosin compared to other antihypertensive agents. 2
Drug Interactions
- Hypotension may develop when prazosin is combined with beta-blockers such as propranolol. 1
- Concurrent use of selective serotonin reuptake inhibitors (SSRIs) may diminish the response to prazosin for PTSD symptoms. 7
Context-Specific Side Effects (PTSD Treatment)
- When used for PTSD nightmares at higher doses (9.5-15.6 mg/day in military veterans), daytime sedation, dizziness, and orthostatic hypotension become more prominent. 3
- Blood pressure monitoring is essential throughout treatment, particularly after initial dosing and with each significant dose increase. 3, 7
Severity and Duration
- The majority (91%) of adverse experiences in mild hypertension are mild-to-moderate in severity. 6
- Most side effects are usually mild and transient, seldom requiring drug discontinuation. 2
- The syncopal adverse effect is self-limiting and typically does not recur after the initial period of therapy or during subsequent dose titration. 1
Risk Mitigation Strategies
- Always start with 1 mg capsules; the 2 mg and 5 mg capsules are not indicated for initial therapy. 1
- Take the initial dose at bedtime to minimize orthostatic effects. 2
- Withhold diuretics for 1 day before initiating prazosin therapy. 2
- Increase dosage slowly and introduce additional antihypertensive drugs with caution. 1
- Patients should be cautioned to avoid situations where injury could result should syncope occur during initiation. 1