Benefit should outweigh risk

AU TGA pregnancy category: C
US FDA pregnancy category: Not assigned

Risk Summary: There is limited data on use of this combination drug or linagliptin alone in pregnant women to inform a drug-associated risk for major birth defects and miscarriage; published studies with metformin have not reported a clear association with major birth defects or miscarriage risk. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy.

Comments:
-If pregnancy is detected, some authorities advise discontinuing this drug and switching to insulin as soon as possible to lower the risk of fetal malformations associated with abnormal blood glucose levels.

Animal studies with linagliptin and metformin have failed to reveal evidence of teratogenicity or effects on prenatal or postnatal development with administration during the period of organogenesis at doses similar to the maximum recommended clinical dose. Linagliptin crosses the placenta following oral dosing in pregnant rats and rabbits. There are no adequate and well controlled studies in pregnant women.

Clinical Considerations:
-Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications and increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. The estimated risk of major birth defects in women with pre-gestational diabetes and a HbA1c greater than 7 has been reported to be between 6% and 10% . This risk has been reported to be as high as 20% to 25% in women with a HbA1c greater than 10.
-Metformin use in premenopausal women may result in ovulation in some anovulatory women.

AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. 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.

See references

There is no information on the clinical use of linagliptin during breastfeeding, but because linagliptin is highly bound, it is unlikely to pass into breastmilk in clinically important amounts. Published studies report that metformin is present in human milk with infant doses of approximately 0.11% to 1% of the maternal weight adjusted dose, but these studies lack the data necessary to evaluate the risks of metformin use during lactation. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for this drug and any potential adverse effects
on the breastfed child from this drug or from the underlying maternal condition.

Safety has not been established

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

Comments:
-The effects in the nursing infant or the effects on milk production are unknown.
-Some authorities advise against use while breastfeeding.

See references