Elexacaftor, Tezacaftor and Ivacaftor use while Breastfeeding
Medically reviewed by Drugs.com. Last updated on Dec 9, 2022.
Elexacaftor, Tezacaftor and Ivacaftor Levels and Effects while Breastfeeding
Summary of Use during Lactation
Information from one maternal-infant pair with ivacaftor and lumacaftor and two pairs with elexacaftor, ivacaftor and tezacaftor indicates that the drugs have low levels in milk and infant serum. An international survey of cystic fibrosis centers found no adverse effects in 26 breastfed infants of mothers taking the elexacaftor, tezacaftor and ivacaftor combination. A task force respiratory experts from Europe, Australia and New Zealand found that these drugs are probably safe during breastfeeding. One breastfed infant had transient elevations in bilirubin and liver enzymes during maternal therapy that could not definitively be attributed to the drugs in breastmilk. Until more data are available, monitoring of infant bilirubin and liver enzymes might be advisable during breastfeeding with maternal elexacaftor, lumacaftor and ivacaftor therapy. Congenital cataracts in breastfed infants has been reported in the infants of mothers who took the drugs during pregnancy. Examination of breastfed infants for cataracts has been recommended. Anecdotal evidence indicates that the drugs in breastmilk may moderate cystic fibrosis in breastfed infants.
Maternal Levels. A woman with cystic fibrosis was treated with lumacaftor and ivacaftor during pregnancy and postpartum. The dosage was not stated, but it was probably the standard dosage of lumacaftor 400 mg and ivacaftor 250 mg orally every 12 hours. The average concentration of ivacaftor in breastmilk samples taken randomly over a 6-month period without regard to the times of the doses was 35.3 mcg/L (0.09 micromolar).
Two nursing mothers with cystic fibrosis who were taking elexacaftor, ivacaftor and tezacaftor, had their milk samples analyzed 2 or 3 times between 15 and 60 days postpartum. Milk levels were all <1 micromolar in one woman at 15 and 60 days postpartum. The other woman had milk levels of the 3 drugs <1 micromolar at 30 days postpartum, milk ivacaftor and tezacaftor levels of <1 micromolar and elexacaftor level of about 1 micromolar at 45 days postpartum. Milk levels of all drugs tended to increase slightly over time.
Two nursing mothers with cystic fibrosis were taking elexacaftor, ivacaftor and tezacaftor in unspecified dosages. The concentrations in milk at unreported times after a dose were ivacaftor 0.03 micromolar (11.8 mcg/L) and 0.26 micromolar (102 mcg/L); tezacaftor levels were 0.12 micromolar (62.5 mcg/L) and 0.39 micromolar (203 mcg/L); and elexacaftor levels were 0.74 micromolar (442 mcg/L) and 1.29 micromolar (771 mcg/L).
Infant Levels. An infant was breastfed by a mother taking lumacaftor and ivacaftor. The percentage of breastfeeding varied between 25% and 100% during this time period. The average infant ivacaftor plasma concentration over the first 6 months of life, excluding day 1 postpartum, was 3.9 mcg/L (0.01 micromolar). This value corresponded to average of 0.5% of simultaneous maternal plasma levels.
Two partially breastfed (extent not stated) infants whose mothers were taking elexacaftor, ivacaftor and tezacaftor had serum drug concentrations measured several times. Tezacaftor levels were highest of the 3 drugs, starting at about 1 micromolar at birth. Levels remained similar in one infant up to 100 days of age and dropped below 1 micromolar at 45 and 60 days postpartum. The levels of the other two drugs dropped to 0.1 micromolar and lower over time.
Effects in Breastfed Infants
A woman with cystic fibrosis was treated with lumacaftor and ivacaftor during pregnancy and postpartum. Her infant was fully breastfed until day 29 postpartum when elevated direct and indirect bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase were found to be elevated. All values had been normal on days 1 and 14. The fraction of breastmilk the infant received was reduced to 25% and all values were normal on day 37. The fraction of breastfeeding was increased to 50% and then to 100%. On day 135, the infant's direct bilirubin was elevated during concurrent maternal levofloxacin and trimethoprim-sulfamethoxazole therapy. The fraction of breastfeeding was decreased to 75% and the direct bilirubin was normal on day 154. The authors noted that the abnormal test results could not definitively be attributed to lumacaftor and ivacaftor therapy.
A survey was sent to lead clinicians of adult CF centers in Europe, the United Kingdom, United States of America, Australia and Israel requesting anonymized data on pregnancy outcomes in women using CFTR modulators during pregnancy and lactation. Responses were received from 31 centers and one woman with CF for a total of 64 pregnancies in 61 women resulting in 60 live births. Thirteen infants were breastfed on ivacaftor alone, 9 infants were breastfed on lumacaftor and ivacaftor, and 5 infants were breastfed on tezacaftor and ivacaftor for a total of 27 infants exposed to ivacaftor in breastmilk, all with no reported complications. The extent of breastfeeding was not reported. An updated survey by the same authors asked CF clinicians to report on pregnant women exposed to the elexacaftor, tezacaftor and ivacaftor combination during pregnancy and breastfeeding. Twenty-six infants were breastfed (extent not stated) during maternal use of the combination. No adverse effects were reported in the breastfed infants.
An infant was born to a mother taking elexacaftor, ivacaftor and tezacaftor for cystic fibrosis. The infant was breastfed (extent not stated). Although the infant had cystic fibrosis-causing CFTR mutations, the infant was healthy and tested negative for cystic fibrosis on newborn screening. The authors expressed concern that the drugs received transplacentally and in breastmilk caused a false negative screening test.
A mother who was a heterozygous carrier of the F508del gene became pregnant with a homozygous infant. At 32 weeks of pregnancy, the mother began elexacaftor, ivacaftor and tezacaftor in the usual adult dosage to treat her fetus who had evidence of meconium ileus. The infant was born at 36 weeks and given pancreatic enzyme replacement therapy with breastfeeding while maternal treatment continued. The infant’s fecal elastase, transaminases and bilirubin were normal at about 1 month of age. The infant’s sweat chloride, although low, was nearer to normal than was expected. The authors hypothesized that the medications received in breastmilk moderated the disease process in the infant.
Three women with cystic fibrosis were taking elexacaftor, ivacaftor and tezacaftor in unspecified dosages during pregnancy and postpartum while breastfeeding. On routine visual examinations between 8 days and 6 months postpartum, their infants were found to have small ( < 1.0 mm) bilateral cataracts, in the central area in one and outside the visual axis in the other two. Breastfeeding was discontinued after diagnosis at 16 days, 9 weeks and 6 months postpartum. The contribution of breastfeeding to the cataracts could not be determined.
Two women were reported by the British Columbia cystic fibrosis clinic who became pregnant and breastfed their infants. One took ivacaftor and breastfed (extent not stated) for 42 months. Her infant was physically normal and healthy, but had speech delay. The other woman took Tricafta (ivacaftor, elexacaftor, and tezacaftor). She breastfed (extent not stated) her infant for 6 months and her infant had no complications.
Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.
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Elexacaftor, Tezacaftor and Ivacaftor
CAS Registry Number
2216712-66-0; 873054-44-5; 1152311-62-0
Chloride Channel Agonists
Cystic Fibrosis Transmembrane Conductance Regulator Protein Modulator
CFTR Protein Modulator
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