Benefit should outweigh risk

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

Risk Summary: Data is limited and incomplete with use of this combination drug or its individual components to inform a drug-related pregnancy risk; reproductive and developmental studies in rats and rabbits have not shown teratogenicity or adverse developmental effects.

While there are no animal studies with concomitant administration of all 3 agents, there are animal studies with the individual agents. Placental transfer of elexacaftor, tezacaftor, and ivacaftor has been observed in pregnant rats; placental transfer of ivacaftor has been observed in pregnant rabbits. Elexacaftor administration to pregnant rats and rabbits during organogenesis demonstrated no teratogenicity or adverse developmental effects at doses that produced maternal exposures up to approximately 2 times the maximum recommended human dose (MRHD) in rats and 4 times the MRHD in rabbits. Tezacaftor administration during organogenesis at doses approximating maternal exposures of up to 3 times (pregnant rats) and 0.2 times (pregnant rabbits) the MRHD revealed no teratogenicity or adverse developmental effects. Ivacaftor administration in rats and rabbits at doses approximating 5 and 14 times MRHD, respectively also revealed no teratogenicity or adverse developmental effects on pups. No adverse developmental effects were observed with administration of elexacaftor or tezacaftor at 1 time the MRHD or ivacaftor at 3 times the MRHD to pregnant rats from organogenesis through lactation. 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.

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There is limited information on the use of elexacaftor, tezacaftor or ivacaftor during breastfeeding and the effects on the breastfed infant, or the effects on milk production. Lacteal excretion has been demonstrated with each component to lactating dams; exposure in rat milk has been estimated to be approximately 0.4, 3, and 1.5 times higher than plasma for elexacaftor, tezacaftor and ivacaftor, respectively. A task force of respiratory experts has looked at these drugs and feels they are probably safe during breastfeeding. Until more data is available, it is important to weigh the developmental and health benefits of breastfeeding along with the mother's clinical need for this drug against any potential adverse effects on the breastfed child from this drug or from the underlying maternal condition.

Benefit should outweigh risk

Excreted into human milk: Elexacaftor (Unknown); Ivacaftor (Yes); Tezacaftor (Unknown)
Excreted into animal milk: Elexacaftor (Yes); Ivacaftor (Yes); Tezacaftor (Yes)

Comments:
-Until more data are available, it may be advisable to monitor bilirubin and liver enzymes of breastfed infants, as well as examine breastfed infants for cataracts.

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