-8 (-11, -4)

 

-8 (-14, -2)

 

-8 (-14, -1)

Supine SBP

 

-4 (-8, 0)

 

-7 (-11, -3)

 

-5 (-9, -2)

 

-3 (-7, 0)

figure 6 

Figure 6: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 10 mg, vardenafil 20 mg or placebo with terazosin (10 mg) in healthy volunteers

 

Figure 7 

Figure 7: Mean change from baseline in standing systolic blood pressure (mmHg) over 6 hour interval following simultaneous or 6 hr separation administration of vardenafil 10 mg, vardenafil 20 mg or placebo with tamsulosin (0.4 mg) in healthy volunteers

 

Effects on Cardiac Electrophysiology

The effect of 10 mg and 80 mg vardenafil on QT interval was eva luated in a single-dose, double-blind, randomized, placebo- and active-controlled (moxifloxacin 400 mg) crossover study in 59 healthy males (81% White, 12% Black, 7% Hispanic) aged 45-60 years. The QT interval was measured at one hour post dose because this time point approximates the average time of peak vardenafil concentration. The 80 mg dose of LEVITRA (four times the highest recommended dose) was chosen because this dose yields plasma concentrations covering those observed upon co-administration of a low-dose of LEVITRA (5 mg) and 600 mg BID of ritonavir. Of the CYP3A4 inhibitors that have been studied, ritonavir causes the most significant drug-drug interaction with vardenafil. Table 6 summarizes the effect on mean uncorrected QT and mean corrected QT interval (QTc) with different methods of correction (Fridericia and a linear individual correction method) at one hour post-dose. No single correction method is known to be more valid than the other. In this study, the mean increase in heart rate associated with a 10 mg dose of LEVITRA compared to placebo was 5 beats/minute and with an 80 mg dose of LEVITRA the mean increase was 6 beats/minute.

Table 6: Mean QT and QTc changes in msec (90% CI) from baseline relative to placebo at 1 hour post-dose with different methodologies to correct for the effect of heart rate. 

 

Drug/Dose

 

QT Uncorrected 

(msec)

 

Fridericia QT 

Correction 

(msec)

Individual QT 

Correction 

(msec)

* Active control (drug known to prolong QT)  

 

 

Vardenafil 10 mg 

 

-2

(-4, 0)

 

8

(6, 9)

 

4

(3, 6)

 

 

Vardenafil 80 mg 

 

-2

(-4, 0)

 

10

(8, 11)

 

6

(4, 7)

 

Moxifloxacina 400 mg* 

 

3

(1, 5)

 

8

(6, 9)

 

7

(5, 8)

 

Therapeutic and supratherapeutic doses of vardenafil and the active control moxifloxacin produced similar increases in QTc interval. This study, however, was not designed to make direct statistical comparisons between the drug or the dose levels. The clinical impact of these QTc changes is unknown [see Warnings and Precautions (5)].