This drug is not recommended during pregnancy based on animal data showing adverse renal effects with empagliflozin administration during a period of renal development that corresponds to the late second and third trimesters of human pregnancy. At doses estimated to be approximately 13-times the maximum human clinical dose, renal, pelvic and tubule dilatations occurred that were reversible. Empagliflozin was not teratogenic in rats and rabbits at doses up to 48 and 128-times, respectively, the maximum human clinical dose when administered during organogenesis. No adverse developmental effects were observed when metformin was administered to pregnant rats and rabbits during the period of organogenesis at doses up to 2 and 6-times, respectively, a 2000 mg clinical dose. In women with pre-gestational diabetes and a HbA1c greater than 7, the estimated background risk of major birth defects is 6% to 10% and for those 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. There are no controlled data in human pregnancy.

Poorly controlled diabetes during pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortion, preterm delivery, stillbirth, and delivery complications; and increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity.

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.

Use is not recommended during the second and third trimesters of pregnancy

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

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

Comments:
-Poorly controlled diabetes during pregnancy increases maternal and fetal risks for adverse outcomes.
-Anovulatory premenopausal women should be informed of the risk for unintended pregnancy as metformin therapy may result in ovulation.

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While it is unknown if empagliflozin 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. Empagliflozin was found in rat milk and appears to accumulate (mean milk to plasma ratio ranging from 0.634 to 5; mean maximal milk to plasma ratio occurring 8 hours postdose). Juvenile rats directly exposed to empagliflozin have shown renal pelvic and tubular dilations during maturation.

Use is not recommended

Excreted into human milk: Yes (metformin); Unknown (empagliflozin)
Excreted into animal milk: Yes (metformin, empagliflozin)

Comments: Breastfeeding is not recommended because of the potential for empagliflozin to affect postnatal renal development.

See references