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 or miscarriage; animal data has shown adverse renal effects with this drug during the renal development period which corresponds to the late second and third trimesters of human pregnancy.

Comments:
-When pregnancy is detected, this drug should be discontinued.
-Poorly controlled diabetes during pregnancy increases maternal and fetal risks for adverse outcomes.

Rat studies have shown adverse renal changes when this drug was administered during the period of renal development corresponding to late second and third trimesters of human development. Renal pelvic and tubule dilations, not fully reversible (within a 1 month recovery period), were observed at all doses studied including the lowest which provided an exposure 15-times the 10 mg clinical dose. There are no adequate well-controlled studies in pregnant women.

Clinical considerations: The estimated background risk of major birth defects is 6% to 10% in women with pre-gestational diabetes with a HbA1c greater than 7% and has been reported to be as high as 20% to 25% in women with HbA1c greater than 10%. Poorly controlled diabetes during pregnancy increases maternal risks for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications; and fetal risks for for major birth defects, stillbirth, and macrosomia related morbidity. Insulin is generally recommended as the drug of choice during pregnancy.

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.

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Not recommended

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

Comment: This drug is not recommended while breastfeeding due to the potential for serious adverse reactions in breastfed infants.

This drug has been found in rat milk at a milk to plasma ratio of 0.49 which means this drug and its metabolites are transferred into milk at a concentration that is approximately 50% of that in maternal plasma. Although, 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 during the first 2 years of life. Juvenile rats directly exposed to this drug have shown renal pelvic and tubular dilations during maturation. The long-term functional consequences of these effects are unknown. Additionally,decreased weight gain has been associated with lactational exposure in juvenile rats.

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