tablets, reported dizziness. Blood pressure effects (standing SBP) in normotensive men on a stable dose of alfuzosin 10 mg following administration of vardenafil 5 mg, vardenafil 10 mg, or placebo separated by 4 hours, are shown in Figure 5.
figure 5
Figure 5: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following 4 hr separation administration of vardenafil 5 mg (stage 1), vardenafil 10 mg (stage 2) or placebo with stable dose alfuzosin 10 mg in BPH patients (Study 3)
Blood pressure effects in normotensive men after forced titration with alpha-blockers:
Two randomized, double blind, placebo-controlled clinical pharmacology studies with healthy normotensive volunteers (age range, 45-74 years) were performed after forced titration of the alpha-blocker terazosin to 10 mg daily over 14 days (n=29), and after initiation of tamsulosin 0.4 mg daily for five days (n=24). There were no severe adverse events related to hypotension in either study. Symptoms of hypotension were a cause for withdrawal in 2 subjects receiving terazosin and in 4 subjects receiving tamsulosin. Instances of outlier blood pressure values (defined as standing SBP <85 mmHg and/or a decrease from baseline of standing SBP >30 mmHg) were observed in 9/24 subjects receiving tamsulosin and 19/29 receiving terazosin. The incidence of subjects with standing SBP <85 mmHg given vardenafil and terazosin to achieve simultaneous Tmax led to early termination of that arm of the study. In most (7/8) of these subjects, instances of standing SBP <85 mmHg were not associated with symptoms. Among subjects treated with terazosin, outlier values were observed more frequently when vardenafil and terazosin were given to achieve simultaneous Tmax than when dosing was administered to separate Tmax by 6 hours. There were 3 cases of dizziness observed with concomitant administration of terazosin and vardenafil. Seven subjects experienced dizziness mainly occurring with simultaneous Tmax administration of tamsulosin. There were no cases of syncope.
Table 5: Mean (95% C.I.) maximal change in baseline in systolic blood pressure (mmHg) following vardenafil 10 and 20 mg in healthy volunteers on daily alpha-blocker therapy
Dosing of Vardenafil and Alpha-Blocker Separated by 6 Hours
Simultaneous dosing of Vardenafil and Alpha-Blocker
Alpha-Blocker
Vardenafil
10 mg
Placebo-Subtracted
Vardenafil
20 mg
Placebo-Subtracted
Vardenafil
10 mg
Placebo-Subtracted
Vardenafil
20 mg
Placebo-Subtracted
* Due to the sample size, confidence intervals may not be an accurate measure for these data. These values represent the range for the difference.
Terazosin
10 mg daily
Standing SBP
-7 (-10, -3)
-11 (-14, -7)
-23 (-31, 16)*
-14 (-33, 11)*
Supine SBP
-5 (-8, -2)
-7 (-11, -4)
-7 (-25, 19)*
-7 (-31, 22)*
Tamsulosin
0.4 mg daily
Standing SBP
-4 (-8, -1)
