From the FDA Drug Label
The effect of 10 mg and 80 mg vardenafil on QT interval was evaluated 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. Table 1 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 1. 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) Moxifloxacin* 400 mg 3(1,5) 8(6,9) 7(5,8)
Vardenafil and QTc:
- Therapeutic doses of vardenafil (10 mg) produced a mean increase in QTc interval of 8 msec (using Fridericia correction) and 4 msec (using individual correction) compared to placebo.
- Supratherapeutic doses of vardenafil (80 mg) produced a mean increase in QTc interval of 10 msec (using Fridericia correction) and 6 msec (using individual correction) compared to placebo.
- The clinical impact of these QTc changes is unknown 1.
From the Research
Vardenafil can prolong the QTc interval, but the effect is typically small and clinically irrelevant at therapeutic doses, with a mean increase of 8 ms at 1 hour after dose, as demonstrated in a well-controlled study 2. The drug inhibits phosphodiesterase type 5 (PDE5) and can cause a modest increase in QTc interval, which becomes clinically significant in patients with pre-existing QT prolongation, electrolyte abnormalities (especially hypokalemia or hypomagnesemia), or in those taking other QT-prolonging medications. Some key points to consider when prescribing vardenafil include:
- Patients with congenital long QT syndrome should avoid vardenafil entirely
- For patients with moderate QTc prolongation (450-500ms), a reduced dose of 5mg may be considered with careful monitoring
- The QT-prolonging effect is dose-dependent, so lower doses carry less risk
- Before prescribing vardenafil, clinicians should obtain a baseline ECG in high-risk patients, correct any electrolyte abnormalities, and review the patient's medication list for potential drug interactions that could further increase QTc
- The mechanism behind vardenafil's QT effect involves delayed cardiac repolarization through effects on potassium channels, which is separate from its therapeutic mechanism for erectile dysfunction It's also important to consider the risk factors for QTc-prolongation, such as hypokalemia, use of diuretics, antiarrhythmic drugs, and QTc-prolonging drugs, as identified in a systematic review 3. Additionally, a study on managing drug-induced QT prolongation in clinical practice provides guidance on how to assess and manage the risk of QT prolongation in patients taking vardenafil 4. Overall, while vardenafil can prolong the QTc interval, the effect is typically small and can be managed with careful monitoring and consideration of individual patient risk factors.