Empagliflozin / linagliptin / metformin Pregnancy and Breastfeeding Warnings

Brand names: Trijardy XR

Medically reviewed by Drugs.com. Last updated on Sep 27, 2023.

Empagliflozin / linagliptin / metformin Pregnancy Warnings

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

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.

This combination 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. Empagliflozin administration at doses estimated to be approximately 13-times the maximum human clinical dose, has shown renal, pelvic and tubule dilatations that are reversible. No adverse developmental effects were observed when linagliptin or metformin were administered to pregnant rats and rabbits. 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. 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; increased fetal risks include major birth defects, still birth, and macrosomia related morbidity.

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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Empagliflozin / linagliptin / metformin Breastfeeding Warnings

Not Recommended

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

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

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.

See references

Further information

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