Interactions between cyclosporine(cycloSPORINE) and Bosentan (bosentan)
cycloSPORINE and bosentan (Major Drug-Drug)
CONTRAINDICATED: Coadministration with cyclosporine may significantly increase the plasma concentrations of bosentan. The proposed mechanism is competitive inhibition of bosentan metabolism via CYP450 3A4 and/or inhibition of intestinal P-glycoprotein secretion by cyclosporine. According to the manufacturer, trough concentrations of bosentan were increased by approximately 30-fold during the first day of concomitant administration, and steady state concentrations were 3- to 4-fold higher than in the absence of cyclosporine. Conversely, the plasma concentrations of cyclosporine decreased by approximately 50%, probably due to induction of CYP450 3A4 by bosentan.
MANAGEMENT: Because elevated plasma levels of bosentan may be associated with increased risk of hepatotoxicity, the concomitant use of cyclosporine and bosentan is considered contraindicated.
