Animal studies have failed to reveal evidence of teratogenicity at high human doses. Decreased fetal body weights in animals were observed at doses of ivacaftor that produced maternal toxicity. Treatment with lumacaftor demonstrated a slight increase in incidence of minor skeletal abnormalities in rabbits at doses that also produced maternal toxicity. Placental transfer of this drug was observed. There are no controlled data in human pregnancy.

AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

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.

This drug should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus.

AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned.

Risk Summary: Limited and incomplete data on use of this drug or its individual components in pregnant women to inform a drug-related risk.

Comments:
-May decrease hormonal contraceptive exposure thus reducing the effectiveness.
-Hormonal contraceptives (including oral, injectable, transdermal, and implantable) should not be relied upon as an effective method of contraception when coadministered with this drug.

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Benefit should outweigh risk

Excreted into human milk: Yes

Comments:
-Effects of this drug on the breastfed infant are unknown; limited data suggests bilirubin and liver enzymes should be monitored in the breastfed infant.
-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 to the breastfed infant from the drug or from the underlying maternal condition.

Data is available from 1 maternal-infant pair. A woman with cystic fibrosis received lumacaftor-ivacaftor during pregnancy and postpartum had breastmilk samples taken randomly over a 6-month period. The average concentrations in breastmilk were lumacaftor: 27.4 mcg/L (0.06 micromolar) and ivacaftor (35.3 mcg/L (0.09 micromolar). Average infant plasma concentrations were lumacaftor: 90.5 mcg/L (0.2 micromolar) and ivacaftor: 3.9 mcg/L (0.01 micromolar), corresponding to 2.7% and 0.5% of maternal plasma levels, respectively. The percentage of infant breastfeeding ranged from 25% to 100%. Breastfeeding was reduced when elevated direct and indirect bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase levels were found. When infant liver tests normalize, the percentage of breastfeeding was increased. The authors of this case report felt the abnormal test results could not be definitively attributed to therapy with this drug, but suggest monitoring infant bilirubin and liver enzymes until more data is available.

See references