Placental transfer of alogliptin into the fetus was observed following oral dosing to pregnant rats.

Pioglitazone

In animal reproductive studies, pregnant rats and rabbits received pioglitazone at doses up to approximately 17 (rat) and 40 (rabbit) times the MRHD based on body surface area (mg/m2); no teratogenicity was observed. Increases in embryotoxicity (increased postimplantation losses, delayed development, reduced fetal weights and delayed parturition) occurred in rats that received oral doses approximately 10 or more times the MRHD (mg/m2 basis). No functional or behavioral toxicity was observed in rat offspring. When pregnant rats received pioglitazone during late gestation and lactation, delayed postnatal development, attributed to decreased body weight, occurred in rat offspring at oral maternal doses approximately two or more times the MRHD (mg/m2 basis). In rabbits, embryotoxicity occurred at oral doses approximately 40 times the MRHD (mg/m2 basis).

8.3 Nursing MothersNo studies have been conducted with the combined components of OSENI. In studies performed with the individual components, both alogliptin and pioglitazone are secreted in the milk of lactating rats. It is not known whether alogliptin and/or pioglitazone are secreted in human milk. Because many drugs are excreted in human milk, and because of the potential for OSENI to cause serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue OSENI, taking into account the importance of OSENI to the mother.

8.4 Pediatric UseSafety and effectiveness of OSENI in pediatric patients have not been established.

OSENI is not recommended for use in pediatric patients based on adverse effects observed in adults, including fluid retention and congestive heart failure, fractures and urinary bladder tumors [see Warnings and Precautions (5.1, 5.5, 5.6, 5.7)].

8.5 Geriatric UseAlogliptin and Pioglitazone

Of the total number of patients (N=1533) in clinical safety and efficacy studies treated with alogliptin and pioglitazone, 248 (16.2%) patients were 65 years and older and 15 (1%) patients were 75 years and older. No overall differences in safety or effectiveness were observed between these patients and younger patients. While this and other reported clinical experiences have not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be excluded.

Alogliptin

Of the total number of patients (N=8507) in clinical safety and efficacy studies treated with alogliptin, 2064 (24.3%) patients were ≥65 years old and 341 (4%) patients were ≥75 years old. No overall differences in safety or effectiveness were observed between patients ≥65 years old and younger patients.

Pioglitazone

A total of 92 patients (15.2%) treated with pioglitazone in the three pooled, 16- to 26-week, double-blind, placebo-controlled, monotherapy trials were ≥65 years old and two patients (0.3%) were ≥75 years old. In the two pooled 16- to 24-week add-on to sulfonylurea trials, 201 patients (18.7%) treated with pioglitazone were ≥65 years old and 19 (1.8%) were ≥75 years old. In the two pooled 16- to 24-week add-on to metformin trials, 155 patients (15.5%) treated with pioglitazone were ≥65 years old and 19 (1.9%) were ≥75 years old. In the two pooled 16- to 24-week add-on to insulin trials, 272 patients (25.4%) treated w