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In vivo drug-drug interaction studies have suggested that Pioglitazone may be a weak inducer of CYP 450 isoform 3A4 substrate. An enzyme inhibitor of CYP2C8 (such as Gemfibrozil) may be significantly increase the AUC of Pioglitazone and an enzyme inducer of CYP2C8 (such as Rifampin) may significantly decrease the AUC of Pioglitazone. Therefore, if an inhibitor or inducer of CYP2C8 is started or stopped during treatment with Pioglitazone, changes in diabetes treatment may be needed based on clinical response.
In vitro, Ketoconazole appears to significantly inhibit the metabolism of Pioglitazone. Patients receiving Ketoconazole concomitantly with Pioglitazone should be evaluated more frequently with respect to glycemic control.
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