The metabolism of pioglitazone involves multiple cytochrome P450 (CYP) isoforms, of which CYP 2C8 (and to lesser degrees, CYP 3A4 and CYP 1A1) have the highest activity. Use of a CYP 2C8 inhibitor (eg, gemfibrozil) may therefore significantly increase the area under the curve (AUC) of pioglitazone; use of a CYP 2C8 inducer (eg, rifampin) may cause a significant decrease.

In a clinical study of 10 healthy volunteers, the addition of oral gemfibrozil (600 mg twice daily) to pioglitazone (30 mg) yielded a 226% increase in pioglitazone exposure (AUC0-24) compared with pioglitazone alone.

A similar study (n = 10) showed that concomitant administration of oral rifampin (600 mg once daily) and pioglitazone (30 mg) resulted in a decrease in the AUC of pioglitazone by 54%.

The FDA notes that if an inhibitor or inducer of CYP 2C8 is started or stopped during treatment with pioglitazone, changes in diabetes treatment may be required based on clinical response.

Pioglitazone tablets are indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. Treatment with pioglitazone/metformin combination tablets is warranted for patients who are inadequately controlled with either component alone or already are receiving both.

Gemfibrozil tablets (Lopid, Pfizer Inc) are indicated as adjunctive therapy for the treatment of adult patients with types 4 and 5 hyperlipidemias who present a risk for pancreatitis and do not respond adequately to diet, and for reducing the risk for de novo coronary heart disease in type 2b patients with lipid abnormalities who have demonstrated inadequate response to weight loss, dietary therapy, exercise, and other pharmacologic agents (eg, bile acid sequestrants and nicotinic acid).
Rifampin capsules and injection (Rifadin and Rifadin IV, Sanofi-Aventis US) are indicated for use as part of a treatment regimen for tuberculosis and for the treatment of asymptomatic carriers of Neisseria meningitidis to eliminate meningococci from the nasopharynx.

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