Pioglitazone and metformin and Topiramate interaction

Pioglitazone and metformin and Topiramate: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Pioglitazone and metformin (Actoplus Met) label · effective 2026-08-21

Major

Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, hepatic…

Boxed warningnames TopiramateView label on DailyMed
Moderate

Topiramate may decrease pioglitazone concentrations.

Drug interactionsnames TopiramateView label on DailyMed
Moderate

Carbonic Anhydrase Inhibitors Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) frequently causes a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis.

Drug interactionsnames TopiramateView label on DailyMed
Moderate

Topiramate A decrease in the exposure of pioglitazone and its active metabolites were noted with concomitant administration of pioglitazone and topiramate [see Clinical Pharmacology (12.3) ] .

Drug interactionsnames TopiramateView label on DailyMed
Moderate

The clinical relevance of this decrease is unknown; however, when ACTOPLUS MET and topiramate are used concomitantly, monitor patients for adequate glycemic control.

Drug interactionsnames TopiramateView label on DailyMed

From the Topiramate (Trokendi XR) label · effective 2026-03-20

Moderate

Pioglitazone A decrease in the exposure of pioglitazone and its active metabolites were noted with the concurrent use of pioglitazone and immediate-release topiramate in a clinical trial.

Drug interactionsnames Pioglitazone and metforminView label on DailyMed
Moderate

The clinical relevance of these observations is unknown; however, when TROKENDI XR is added to pioglitazone therapy or pioglitazone is added to TROKENDI XR therapy, careful attention should be given to the routine monitoring of patients for adequate control of their diabetic disease state [see Clinical Pharmacology (12.3) ] .

Drug interactionsnames Pioglitazone and metforminView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.