Animal studies have revealed evidence of adverse renal changes. Rats receiving doses approximately 13 times the maximum clinical dose during a period of renal development (corresponding to late second and third trimester of human pregnancy) experienced renal pelvic and tubule dilations and renal mineralization that were not fully reversible. There was no evidence of fetal harm in rats or rabbits exposed to approximately 300 times the clinical dose when administered during organogenesis. There are no controlled data in human pregnancy.

Clinical Considerations: Poorly controlled diabetes during pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth, and delivery complications; poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. In women with pre-gestational diabetes and a HbA1c greater than 7, the estimated background risk of major birth defects is 6% to 10%. For women with a HbA1c greater than 10, the risk may be as high as 20% to 25%. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

Not recommended during the second and third trimesters of pregnancy

AU TGA pregnancy category: D
US FDA pregnancy category: Not Assigned

Risk Summary: There is insufficient data in pregnant women to determine a drug-associated risk for major birth defects and miscarriage; animal data has shown adverse renal effects with administration during the renal development period which corresponds to the late second and third trimesters of human pregnancy.

Comment: Poorly controlled diabetes during pregnancy increases maternal and fetal risks of adverse outcomes.

See references

Not recommended

Excreted into human milk: Unknown
Excreted into animal milk: Yes

Comment: Women should be advised to avoid breastfeeding because of the potential for this drug to affect postnatal renal development.

While it is unknown if this drug is excreted into human milk, there is potential for serious harm to the developing kidney if the breastfed infant is exposed. Human kidney maturation occurs in utero and during the first 2 years of life. This drug was found in rat milk. An increased risk to the developing kidney (persistent increased organ weight, renal mineralization, renal pelvic and tubular dilations) has been observed in juvenile rats directly exposed to this drug during a developmental period corresponding to human kidney maturation.

See references