1. Aschenbrenner, Diane S. MS, RN


* Trikafta, a combination of elexacaftor, ivacaftor, and tezacaftor, is a new drug for the treatment of the most common cystic fibrosis mutation.


* Serious adverse effects include elevated liver enzymes and an increased risk of cataracts.



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The Food and Drug Administration (FDA) has approved Trikafta, the first triple combination therapy (elexacaftor-ivacaftor-tezacaftor) to treat patients with the most common cystic fibrosis mutation. The treatment regimen requires a dose of Trikafta in the morning and a separate dose of ivacaftor, as monotherapy, in the evening. Trikafta can be used in patients 12 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (about 90% of those with cystic fibrosis).


Trikafta targets the defective CFTR protein made by the defective gene and helps it to function. Elexacaftor and tezacaftor bind to different sites on the CFTR protein, creating an additive effect and delivering more CFTR protein to the cell surface than either drug would do alone. Ivacaftor helps to open the channel of the CFTR protein at the cell surface. This combined activity increases CFTR activity. Trikafta comes in a blister pack containing both the combination product and individual ivacaftor tablets.


In two clinical trials, with a total of 510 patients, Trikafta significantly increased the percent predicted forced expiratory volume in one second (ppFEV1)-an established marker of cystic fibrosis progression-by between 10% and 13.8% from baseline.


Serious adverse effects of Trikafta include liver enzyme elevations and cataracts, which have been reported in patients treated with ivacaftor-containing products. The most common adverse effects include headaches, respiratory and other infections (upper respiratory tract infections, rhinorrhea and/or rhinitis, influenza, sinusitis, nasal congestion), gastrointestinal effects (abdominal pain, diarrhea), rash, elevated liver enzymes, increased creatine phosphokinase levels, and elevated bilirubin levels.


Drug interactions can occur with drugs that are strong inducers of the cytochrome P-450 (CYP) isoenzyme CYP3A (such as rifampin or St. John's wort). Coadministration with these drugs can significantly decrease the circulating levels of Trikafta. Coadministration with moderate or strong inhibitors of CYP3A may increase the circulating levels of Trikafta and require dose adjustments.


Nurses should complete a thorough medication assessment to determine if the patient is currently receiving any drug that could interact with Trikafta. If present, nurses should notify the prescriber, as concomitant use of CYP3A inducers is not recommended and moderate to strong inhibitors of CYP3A may require a dose adjustment. Because of the risk of elevated liver enzymes, nurses should confirm that liver enzymes and bilirubin levels are assessed prior to starting Trikafta.


Patients and families should be taught about the importance of returning for blood work every three months during the first year of treatment and annually thereafter. Any signs of liver damage (pain or discomfort in the right upper abdomen, nausea or vomiting, yellowing of the skin or sclera, dark-colored urine, or loss of appetite) should be reported to the health care provider. The need for baseline and follow-up eye examinations related to the risk of cataracts should be explained to patients and their families. Nurses should teach patients and families to take two tablets of Trikafta in the morning, swallowed whole, with a fat-containing food (such as food containing butter, oil, eggs, cheese, nuts, whole milk, or meat). The patient should take the ivacaftor dose approximately 12 hours later.


For full prescribing information for Trikafta, go to