What alpha blockers (e.g. doxazosin, terazosin, prazosin) cannot be mixed with Phosphodiesterase 5 (PDE5) inhibitors?

Alpha-Blockers That Require Caution with PDE5 Inhibitors

Doxazosin, prazosin, and terazosin are the alpha-blockers that cannot be safely mixed with PDE5 inhibitors without significant risk of symptomatic hypotension, while tamsulosin (0.4 mg) has minimal hemodynamic interaction and can be safely combined. 1, 2

Critical Drug-Specific Interactions

High-Risk Alpha-Blockers (Avoid or Use Extreme Caution)

Doxazosin is explicitly contraindicated for routine combination with PDE5 inhibitors due to additive blood pressure lowering effects and symptomatic hypotension. 1

• The FDA label specifically warns that concomitant administration of doxazosin with a PDE5 inhibitor results in additive blood pressure lowering effects and symptomatic hypotension. 1
• Clinical trial data demonstrates that tadalafil 20 mg augmented the hypotensive effect of doxazosin 8 mg, producing a mean maximal decrease in standing systolic BP of 9.8 mm Hg greater than placebo. 2
• 28% of subjects taking doxazosin plus tadalafil experienced standing systolic BP less than 85 mm Hg, compared to only 6% on doxazosin plus placebo. 2
• Sildenafil with doxazosin has been documented to evoke orthostatic hypotension in some patients. 2

Terazosin similarly causes orthostatic hypotension when combined with PDE5 inhibitors. 2

• Vardenafil given with terazosin evokes orthostatic hypotension in some patients. 2
• Terazosin is associated with orthostatic hypotension, especially in older adults, and this risk is compounded when combined with PDE5 inhibitors. 3

Prazosin carries the same risks as other non-selective alpha-1 blockers when combined with PDE5 inhibitors. 3, 4

• Prazosin is associated with orthostatic hypotension, especially in elderly patients, and requires 2-3 times daily dosing. 3, 4
• The first dose should be administered at bedtime to reduce the risk of first-dose syncope, a risk that would be amplified with concurrent PDE5 inhibitor use. 4, 5

Safe Alternative: Tamsulosin

Tamsulosin 0.4 mg is the only alpha-blocker that can be safely combined with PDE5 inhibitors without significant hemodynamic interaction. 2

• Tadalafil 10 and 20 mg produced mean maximal decreases in standing systolic BP similar to placebo when combined with tamsulosin (mean difference of only 1.7 and 2.3 mm Hg, respectively). 2
• No subject taking tamsulosin had a decrease in standing systolic BP less than 85 mm Hg when combined with tadalafil. 2
• In patients taking tadalafil for ED, tamsulosin 0.4 mg may be given for the treatment of benign prostatic hyperplasia. 2

Clinical Management Algorithm

If Patient Requires Both Alpha-Blocker and PDE5 Inhibitor:

1. Switch to tamsulosin 0.4 mg as the alpha-blocker of choice if the patient is on doxazosin, terazosin, or prazosin. 2

2. If tamsulosin is contraindicated or ineffective, use the lowest doses of both medications and monitor blood pressure closely:

   • Start with the lowest dose of the PDE5 inhibitor. 6
   • Monitor standing and supine blood pressure before and after dosing. 2
   • Warn patients about orthostatic symptoms and advise them to rise slowly from sitting or lying positions. 1

3. Avoid combination therapy entirely in elderly patients or those with baseline orthostatic hypotension. 3, 6

Common Pitfalls to Avoid

• Do not assume all alpha-blockers are equivalent: The hemodynamic interaction varies dramatically between non-selective alpha-1 blockers (doxazosin, terazosin, prazosin) and the uroselective tamsulosin. 2
• Do not ignore the timing of doses: Even with tamsulosin, consider separating administration times to minimize any potential additive effects. 6
• Do not prescribe without patient education: Patients must understand the risk of dizziness, lightheadedness, and syncope, particularly when standing quickly. 1
• Do not overlook baseline cardiovascular status: Greater declines in blood pressure may occur in treated and untreated hypertensive patients. 6