There are no animal studies with the concomitant administration of both agents, but animal studies are available with the individual agents. Tezacaftor administration during organogenesis at doses approximating maternal exposures of up to 3 times (pregnant rats) and 0.2 times (pregnant rabbits) the maximum recommended human dose (MRHD) revealed no teratogenicity or adverse developmental effects. Ivacaftor administration in rats and rabbits at doses approximating 6 and 16 times MRHD, respectively also revealed no teratogenicity or adverse developmental effects on pups. No adverse developmental effects were observed with administration of either tezacaftor at 1 time the MRHD or ivacaftor at 4 times the MRHD to pregnant rats from organogenesis through lactation. At maternally toxic doses (i.e., tezacaftor 2 times the MRHD; ivacaftor 6 times MRHD), decreased fetal body weights and early developmental delays in pinna detachment, eye opening, and righting reflex occurred with tezacaftor and decreased fetal body weight was observed with ivacaftor. 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.

Benefit should outweigh risk

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

Risk Summary: Data is limited and incomplete on 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.

Comments: Some authorities advice against use during pregnancy as a precautionary measure.

See references

Benefit should outweigh risk

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

Comments: The effects in the nursing infant are unknown.

There is no information on the presence of either tezacaftor or ivacaftor in human milk, the effects on the breastfed infant, or the effects on milk production. Lacteal excretion has been demonstrated following single dose administration to lactating dams. Exposure in milk has been estimated to be approximately 3 times and 1.5 times higher than plasma for tezacaftor and ivacaftor, respectively. When evaluating the risks and benefits it is important to consider 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.

See references