Actos

[Pioglitazone]

Excretion and Elimination:

Following oral administration, approximately 15% to 30% of the pioglitazone dose is recovered in the urine. Renal elimination of pioglitazone is negligible, and the drug is excreted primarily as metabolites and their conjugates. It is presumed that most of the oral dose is excreted into the bile either unchanged or as metabolites and elim-inated in the feces. The mean serum half-life of pioglitazone and total pioglitazone ranges from 3 to 7 hours and 16 to 24 hours, respectively. Pioglitazone has an apparent clearance, CL/ F, calculated to be 5 to 7 L/ hr.

Special Populations

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Renal Insufficiency:

The serum elimination half-life of pioglitazone, M-III, and M-IV remains unchanged in patients with moderate (creatinine clearance 30 to 60 mL/ min) to severe (creatinine clearance < 30 mL/ min) renal impairment when compared to normal subjects. No dose adjustment in patients with renal dysfunction is recommended (see DOSAGE AND ADMINISTRATION).

Hepatic Insufficiency:

Compared with normal controls, subjects with impaired hepatic function (Child-Pugh Grade B/ C) have an approximate 45% reduction in pioglitazone and total pioglitazone mean peak concentrations but no change in the mean AUC values. ACTOS therapy should not be initiated if the patient exhibits clinical evidence of active liver disease or serum transaminase levels (ALT) exceed 2.5 times the upper limit of normal (see PRECAUTIONS, Hepatic Effects).

Elderly:

In healthy elderly subjects, peak serum concentrations of pioglitazone and total pioglitazone are not significantly different, but AUC values are slightly higher and the terminal half-life values slightly longer than for younger subjects. These changes were not of a magnitude that would be considered clinically relevant.

Pediatrics:

Pharmacokinetic data in the pediatric population are not available.

Gender:

The mean Cmax and AUC values were increased 20% to 60% in females. As monotherapy and in combination with sulfonylurea, metformin, or insulin, ACTOS improved glycemic control in both males and females. In controlled clinical trials, hemo-globin A1c (HbA1c) decreases from baseline were generally greater for females than for males (average mean difference in HbA1c 0.5%). Since therapy should be individualized for each patient to achieve glycemic control, no dose adjustment is recommended based on gender alone.

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