Women’s lung health
Pregnancy in cystic fibrosis
The newest in the line of modulator therapy, Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor), is expected to improve life expectancy and quality of life for patients with cystic fibrosis (CF). This evolution in therapy will shape how providers care for their patients, particularly women of reproductive age. Conventionally, women with significantly impaired lung function due to CF have been advised to avoid pregnancy due to potential complications for mother and baby. It is likely that now, with improved lung function while receiving Trikafta, more women will feel better equipped to attempt pregnancy.
Dr. Debasree Banerjee
There are several considerations in this setting, including the need for careful drug safety and monitoring, creating a plan of action for possible decline in lung function while off certain CF-related medications, and counseling on drug interactions during lactation. In our experience with women becoming pregnant while receiving Trikafta or contemplating pregnancy, all have opted to discontinue modulator therapy with declines in lung function. Trikafta does not report teratogenicity based on animal studies of the individual components of the drug; however, ivacaftor is known to cause impairment in fertility and reproductive indices, including nonviable embryos and implantation failure in a rat model at five times the maximum recommended human dose, dosed prior to and during early embryogenesis. Small mammal models have decreased birth weight at high doses of elexacaftor, tezacaftor and ivacaftor administered individually. There is evidence of placental transfer of ivacaftor and breast milk concentrations of tezacaftor and ivacaftor are higher than plasma concentrations in rats. There are no human data in parturient or lactating women or infants. Three women became pregnant during the phase 3 clinical study of Trikafta, one with elective termination, one pregnancy was carried to full term with normal birth outcome, and one ended in a spontaneous abortion, which was deemed not to be related to the study drug. Translating this information into recommendations for patients has important implications.
Debasree Banerjee, MD, MS
Steering Committee Member