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In vivo drug-drug interaction studies have suggested that pioglitazone may be a weak inducer of CYP450 isoform 3A4 substrate (see Pharmacology: Pharmacokinetics: Drug-Drug Interactions under Actions).
An enzyme inhibitor of CYP2C8 (such gemfibrozil) may significantly increase the AUC of pioglitazone and an enzyme inducer of CYP2C8 (such rifampicin) 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 (see Pharmacology: Pharmacokinetics: Drug-Drug Interactions under Actions).
Hypoglycemia may occur when pioglitazone is administered with a sulfonylurea or insulin. Patients receiving pioglitazone in combination with insulin or other antidiabetic medications (particularly insulin secretagogues such as sulfonylureas) may be at risk of hypoglycemia.
