Interactions between micronase(glyBURIDE) and Bosentan (bosentan)
glyBURIDE and bosentan (Major Drug-Drug)
CONTRAINDICATED: In the REACH-1 trial, an increased incidence of elevated liver transaminases was observed in the subgroup of patients receiving bosentan in combination with glyburide relative to the bosentan group as a whole or those receiving placebo (28.6%, 17.6%, and 4%, respectively). The exact mechanism of interaction is unknown but may be partially due to additive inhibition of the hepatocellular bile salt export pump, resulting in increased hepatocyte concentrations of toxic bile salts. In REACH-1, bosentan-induced elevations in liver transaminase levels were asymptomatic and reversible and did not result in any signs of clinically significant liver disease. Pharmacokinetically, coadministration of the two drugs can result in decreased plasma concentrations of both. In 12 healthy volunteers given bosentan (125 mg orally twice a day) and glyburide (2.5 mg orally twice a day), the area under the plasma concentration-time curve (AUC) of bosentan and its metabolites decreased by 20% to 30%, and that of glyburide decreased by 40%.
MANAGEMENT: According to the manufacturer, the concomitant use of glyburide and bosentan is contraindicated. Alternative hypoglycemic agents should be considered.
