Actos - Clinical Pharmacology

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Special Populations

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.

Ethnicity:

Pharmacokinetic data among various ethnic groups are not available.

Drug-Drug Interactions

The following drugs were studied in healthy volunteers with a co-administration of ACTOS 45 mg once daily. Listed below are the results: