Drug Interactions between Actos and resmetirom

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 2C8 may increase the plasma concentrations of pioglitazone, 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 30 mg dose of pioglitazone on day 3, mean pioglitazone systemic exposure (AUC) increased by 3.4-fold and elimination half-life (T 1/2) increased from 6.5 to 15.1 hours. In two other studies of 12 and 30 healthy volunteers, gemfibrozil administered similarly increased the mean AUC of a single 15 mg dose of pioglitazone by 3.2- and 4.3-fold, respectively, and nearly tripled the mean T 1/2. When 160 mg twice daily of trimethoprim, a relatively weak CYP450 2C8 inhibitor, was given similarly in a study of 16 healthy volunteers, the mean AUC of a 15 mg dose of pioglitazone increased by 42% and T 1/2 increased from 3.9 to 5.1 hours. Likewise, administration of pioglitazone with a single 1000 mg dose of abiraterone acetate, another CYP450 2C8 inhibitor, resulted in a 46% increase in pioglitazone AUC. The interaction is subject to a high degree of interpatient variability, which may be at least partially attributable to CYP450 2C8 polymorphism.

MANAGEMENT: Given the potential for dose-related adverse events with pioglitazone, caution is advised during coadministration with CYP450 2C8 inhibitors. 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; 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 pioglitazone 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 pioglitazone dosage adjusted as necessary.