Drug Interactions between Avandia and resmetirom

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 2C8 may increase the plasma concentrations of rosiglitazone, which is primarily metabolized by the isoenzyme. In 10 healthy volunteers given the potent CYP450 2C8 inhibitor gemfibrozil (600 mg twice daily) for two days prior to coadministration with a single 4 mg dose of rosiglitazone on day 3, mean rosiglitazone systemic exposure (AUC) increased by 127% and elimination half-life from 3.6 to 7.6 hours, while the plasma concentration measured 24 hours after dosing increased by 9.8-fold. In 10 healthy volunteers given the less potent CYP450 2C8 inhibitor trimethoprim (160 mg orally twice a day) for 4 days prior to coadministration with a single 4 mg dose of rosiglitazone, mean AUC of rosiglitazone increased by 37% and half-life from 3.8 to 4.8 hours. Nearly identical results were reported in eight healthy volunteers in another study administered trimethoprim and rosiglitazone.

MANAGEMENT: Given the potential for dose-related adverse events with rosiglitazone, caution is advised during coadministration with CYP450 2C8 inhibitors, particularly in patients already receiving a higher dosage of rosiglitazone (e.g., 8 mg/day). Close monitoring for the development of hypoglycemia and other adverse effects is recommended, such as fluid retention; weight gain; new or worsening heart failure; pulmonary, peripheral, and macular edema; angina; bone fractures; anemia; and liver enzyme elevations. Patients should regularly monitor their blood sugar and learn how to recognize and treat hypoglycemia, which may include symptoms such as headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, and palpitation. The dosage of rosiglitazone may require adjustment if an interaction is suspected. Likewise, patients should be observed for potential loss of glycemic control following discontinuation of the CYP450 2C8 inhibitor, and the rosiglitazone dosage adjusted as necessary.