Grapefruit juice can affect the
pharmacokinetics of sildenafil (AUC increased by 23%), probably by inhibiting the
metabolism on sildenafil by CYP3A4. Tadalafil and vardenafil are predicted to interact similarly.
It has been suggested that although the pharmacokinetic changes are unlikely to be clinically significant, the combination is best avoided because concurrent use results in an increased variability in sildenafil
pharmacokinetics. However, this seems over-cautious, as reduced doses of sildenafil can be given with more potent CYP3A4 inhibitors. The manufacturers of
tadalafil and vardenafil advise caution and avoidance, respectively, in those who drink
grapefruit juice.