) compared to healthy subjects. The magnitude of these reductions is not considered to be clinically meaningful. Patients with severe hepatic impairment (Child-Pugh Grade C) have not been studied. Use caution when administering OSENI to patients with liver disease [see USE IN SPECIFIC POPULATIONS (8.6) and WARNINGS AND PRECAUTIONS (5.4)].
Pioglitazone
Compared with healthy controls, subjects with impaired hepatic function (Child-Pugh Grade B and C) have an approximate 45% reduction in pioglitazone and total pioglitazone (pioglitazone, M-III and M-IV) mean peak concentrations but no change in the mean AUC values. Therefore, no dose adjustment in patients with hepatic impairment is required.
There are postmarketing reports of liver failure with pioglitazone and clinical trials have generally excluded patients with serum ALT >2.5 times the upper limit of the reference range. Use caution in patients with liver disease [see WARNINGS AND PRECAUTIONS (5.4)].
Gender
Alogliptin
No dose adjustment of alogliptin is necessary based on gender. Gender did not have any clinically meaningful effect on the pharmacokinetics of alogliptin.
Pioglitazone
The mean Cmax and AUC values of pioglitazone were increased 20% to 60% in women compared to men. In controlled clinical trials, A1C decreases from baseline were generally greater for females than for males (average mean difference in A1C 0.5%). Because therapy should be individualized for each patient to achieve glycemic control, no dose adjustment is recommended based on gender alone.
Geriatric
Alogliptin
No dose adjustment of alogliptin is necessary based on age. Age did not have any clinically meaningful effect on the pharmacokinetics of alogliptin.
Pioglitazone
In healthy elderly subjects, peak serum concentrations of pioglitazone and total pioglitazone are not significantly different, but AUC values are approximately 21% higher than those achieved in younger subjects. The mean terminal half-life values of pioglitazone were also longer in elderly subjects (about 10 hours) as compared to younger subjects (about seven hours). These changes were not of a magnitude that would be considered clinically relevant.
Pediatrics
Alogliptin
Studies characterizing the pharmacokinetics of alogliptin in pediatric patients have not been performed.
Pioglitazone
Safety and efficacy of pioglitazone in pediatric patients have not been established. Pioglitazone is not recommended for use in pediatric patients [see USE IN SPECIFIC POPULATIONS (8.4)].
Race and Ethnicity
Alogliptin
No dose adjustment of alogliptin is necessary based on race. Race (White, Black and Asian) did not have any clinically meaningful effect on the pharmacokinetics of alogliptin.
Pioglitazone
Pharmacokinetic data among various ethnic groups are not available.
Drug Interactions
Coadministration of alogliptin 25 mg once daily with a CYP2C8 substrate, pioglitazone 45 mg once daily for 12 days had no clinically meaningful effects on the pharmacokinetics of pioglitazone and its active metabolites.
Specific pharmacokinetic drug interaction studies with OSENI have not been performed, although such studies have been conducted with the individual components of OSENI (alogliptin and pioglitazone).
Alogliptin
In Vitro Assessment of Drug Interactions
In vitro studies indicate that alogliptin is neit
