Ketoconazole increases
bosentan levels 2-fold, but the
clinical significance of this is unclear. Fluconazole and
voriconazole are predicted to have a greater effect.
As elevated
bosentan levels are associated with an increased risk of liver
toxicity the manufacturers do not recommend the concurrent use of
azoles (particularly fluconazole). If the combination is used it may be prudent to monitor liver function closely. The manufacturers suggest that no dosage adjustment is likely to be required if
ketoconazole were to be used with
bosentan.