MajorLipid-lowering agent of the fibrate class×Thiazolidinedione (PPAR-γ agonist), oral antidiabetic
Updated · Methodology
Mechanism
Pioglitazone is metabolised mainly by CYP2C8, and gemfibrozil is a strong inhibitor of that enzyme. Pioglitazone exposure rises, and its dose-dependent effects intensify with it: fluid retention and weight gain.
Symptoms
Ankle oedema, rapid weight gain, breathlessness on exertion and when lying down as a sign of decompensating heart failure. Hypoglycemia is possible when pioglitazone is taken with insulin or a sulfonylurea.
Management
The pioglitazone dose is reduced, as the label's general rule for CYP2C8 substrates requires. Weight and oedema are monitored from the first weeks of joint use. The combination is not used in heart failure.
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Sources
- FDA: LOPID (gemfibrozil tablets, USP) prescribing information (2024)– FDA DailyMed, LOPID (gemfibrozil), Parke-Davis Div of Pfizer, 2024
- AEMPS: Ficha técnica: Gemfibrozilo (nº registro 61831), sección 4.5 (2025)– AEMPS, CIMA, nº registro 61831, revisión 05/2025, sección 4.5
- AEMPS: Ficha técnica: Pioglitazona (nº registro 75153), sección 4.5 (2021)– AEMPS, CIMA, nº registro 75153, revisión 10/2021, sección 4.5