No adverse developmental effects were observed when canagliflozin and metformin were co-administered to pregnant rats during the period of organogenesis at exposures up to 11 and 13 times the expected human doses, respectively. Canagliflozin drug exposure during periods of animal development corresponding to the late second and third trimesters of human development, showed increased kidney weights and renal pelvic and tubular dilation at doses expected during human exposure. The renal pelvic dilatations observed did not fully reverse within a 1-month recovery period. 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 adequate and well-controlled studies in pregnant women.

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

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 canagliflozin 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.

See references

Not recommended

Excreted into human milk: Unknown (canagliflozin); Yes, in small amounts (metformin)
Excreted into animal milk: Yes (canagliflozin, metformin)

Comments:
-Because of the potential for serious adverse reactions in the nursing infant, breastfeeding is not recommended while taking this drug.

Upon administering radiolabeled canagliflozin to lactating rats, a milk to plasma ratio of 1.4 was found indicating that canagliflozin may be transferred into milk at a concentration comparable to that in plasma. Since human kidney maturation occurs in utero and during the first 2 years of life (when lactational exposure may occur), there may be a risk to the developing human kidney. A risk to the developing rat kidney (renal pelvic and tubular dilations) was observed when juvenile rats were exposed to canagliflozin during maturation.

See references