Oseni Use In Pregnancy & Lactation

Use in Pregnancy: Pregnancy Category C: Alogliptin and Pioglitazone: There are no adequate and well-controlled studies in pregnant women with OSENI or its individual components. Based on animal data, the likelihood that OSENI increase the risk of developmental abnormalities is predicted to be low. OSENI should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
When administered to rats during organogenesis the combination treatment with alogliptin and pioglitazone (100 mg/kg alogliptin plus 40 mg/kg pioglitazone) slightly augmented pioglitazone-related fetal effects of delayed development and reduced fetal weights, but did not result in embryo-fetal mortality or teratogenicity.
Alogliptin: Alogliptin, administered to pregnant rabbit and rats during the period of organogenesis was not teratogenic at doses of up to 200 and 500 mg/kg, or 149-times and 180-times, respectively, the clinical dose based on plasma drug exposure (AUC).
Doses of alogliptin up to 250 mg/kg (approximately 95-times clinical exposure based on AUC) given to pregnant rats from gestation day 6 to lactation day 20 did not harm the developing embryo or adversely affect growth and development of offspring.
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 2 or more times the MRHD (mg/m² basis). In rabbits, embryotoxicity occurred at oral doses approximately 40 times the MRHD (mg/m² basis).
Use in Lactation: No 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.