Gender

Alogliptin

No dose adjustment 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 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 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 neither an inducer of CYP1A2, CYP2B6, CYP2C9, CYP2C19 and CYP3A4, nor an inhibitor of CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP3A4 and CYP2D6 at clinically relevant concentrations.

In Vivo Assessment of Drug Interactions

Effects of Alogliptin on the Pharmacokinetics of Other Drugs

In clinical studies, alogliptin did not meaningfully increase the systemic exposure to the following drugs that are metabolized by CYP isozymes or excreted unchanged in urine (Figure 1). No dose adjustment of alogliptin is recommended based on results of the described pharmacokinetic studies.

Figure 1. Effect of Alogliptin on the Pharmacokinetic Exposure to Other Drugs

*Warfarin was given once daily at a stable dose in the range of 1 mg to 10 mg. Alogliptin had no significant effect on the prothrombin time (PT) or International Normalized Ratio (INR).

**Caffeine (1A2 substrate), tolbutamide (2C9 substrate)