No reports describing the use of pioglitazone during human pregnancy have been located. Insulin is the treatment of choice for pregnant diabetic patients because, in general, other hypoglycemic agents do not provide adequate glycemic control. Moreover, insulin, unlike most oral agents, does not cross the placenta to the fetus, thus eliminating the additional concern that the drug therapy itself will adversely affect the fetus. Carefully prescribed insulin therapy provides better control of the mother's glucose, thereby preventing the fetal and neonatal complications that occur with this disease. High maternal glucose levels, as may occur in diabetes mellitus, are closely associated with a number of maternal and fetal adverse effects, including fetal structural anomalies if the hyperglycemia occurs early in gestation. To prevent this toxicity, the American College of Obstetricians and Gynecologists recommends that insulin be used for types 1 and 2 diabetes occurring during pregnancy and, if diet therapy alone is not successful, for gestational diabetes (1,2).
No reports describing the use of pioglitazone during human lactation have been located. The molecular weight of pioglitazone (about 357 for the free base) is low enough that secretion into breast milk should be expected. At least three active metabolites have been identified, and these also may be transferred into milk. The effect on a nursing infant from these exposures is unknown. However, weak bases are known to accumulate in milk with concentrations higher than those in maternal plasma. The most common adverse reactions observed in adults were upper respiratory tract infection, headache, sinusitis, myalgia, and pharyngitis (1). If a woman is receiving this drug while breastfeeding, her nursing infant should be monitored for these effects.
Pioglitazone (Actos)
Pregnancy Recommendation:No Human Data—Animal Data Suggest Moderate Risk
Breastfeeding Recommendation:No Human Data—Probably Compatible
Pioglitazone, a thiazolidinedione antidiabetic agent, is used as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. It is used either alone or in combination with other antidiabetic agents (insulin, metformin, or sulfonylureas). Pioglitazone is not an insulin secretagogue but acts to decrease insulin resistance in the periphery and in the liver (i.e., decreases insulin requirements). It requires the presence of insulin for its action. Pioglitazone undergoes extensive metabolism by hydroxylation and oxidation, and at least three of the metabolites are pharmacologically active. It is >98% bound to plasma proteins and has an elimination half-life of pioglitazone, and its metabolites are 3-7 hours and 16-24 hours, respectively (3).
Animal Data: Reproduction studies with pioglitazone have been conducted in rats and rabbits at doses up to 17 and 40 times, respectively, the maximum recommended human dose based on BSA (MRHD) (1). In pregnant rats, at ≥10 times the MRHD, pioglitazone was embryotoxic as evidenced by increased postimplantation losses, delayed development, and reduced fetal weights. At ≥2 times the MRHD during late gestation and in the lactation period, delayed development was observed that was attributed to decreased body weights. Embryotoxicity was observed in rabbits dosed at 40 times the MRHD (3).
Placental Transfer: It is not known if pioglitazone or its active metabolites cross the placenta to the fetus. The molecular weight of the parent compound (about 357 for the free base) is low enough that transfer to the fetus should be expected.