Trikafta (elexacaftor/ tezacaftor/ivacaftor)
Trikafta is a combination drug that includes three different drugs: elexacaftor, tezacaftor, and ivacaftor. Trikafta belongs to a class of drugs called CFTR modulators. It is designed for people with cystic fibrosis (CF) who have at least one of 178 different mutations in their CFTR (cystic fibrosis transmembrane conductance regulator) gene. This includes the most common mutation, F508del.1 Trikafta is the first triple therapy for CF, and is recommended for those at least 12 years and older.
In the EU, Trikafta is referred to as Kaftrio.
What are the ingredients in Trikafta?
The main ingredients in Trikafta are elexacaftor, tezacaftor, and ivacaftor. Elexacaftor and tezacaftor are CFTR correctors, while ivacaftor is a potentiator.
How does Trikafta work?
Trikafta is a combination of two CFTR correctors and a potentiator. People with CF have a mutation in their CFTR gene. This gene is responsible for a certain protein that creates a channel, or gateway, so that chloride can pass in and out of the body’s cells. When this channel does not work, it can affect salt and water balance. This can lead to thick mucus building up in the lungs, pancreas, and other parts of the body.
CFTR correctors, like elexacaftor and tezacaftor, help the channel work better. CFTR potentiators, like ivacaftor, help keep the corrected channel open so chloride can pass through. Both of these mechanisms can help improve salt and water balance and thin out mucus. Although the CFTR channel is not completely corrected, improving its function in this way can help reduce CF-related symptoms. Fewer symptoms may reduce the number of CF exacerbations.
What are the possible side effects of Trikafta?
The most common side effects of Trikafta include:
- Abdominal pain
- Upper respiratory infections
- Nasal congestion
- Runny nose or nasal inflammation
- Sinus infections
- Increased amounts of creatinine kinase in the blood (a protein that is used by muscle cells)
This is not a complete list of side effects. Talk to your doctor about the drugs you’re currently taking to avoid potential drug interactions.
Things to know about Trikafta
Trikafta can cause increased liver function test results, including ALT (alanine aminotransferase), AST (aspartate aminotransferase), and bilirubin. When these test results are high, it may mean that the liver is not working as well as it should.
Liver function tests (LFTs) should be done every 3 months for the first year after starting Trikafta. After the first year, some people may only need to be tested once a year. However, people with a history of liver or gallbladder issues may need to be tested more often. In some cases, these people may not be able to take Trikafta. If liver function tests become too abnormal, the dosage of Trikafta may need to be changed or stopped completely.
Signs that something may be wrong with your liver include:
- Pain in the upper right stomach area
- Nausea or vomiting
- Dark-colored urine
- Yellowing of the skin or whites of the eyes
- Loss of appetite
This is not a complete list of all liver-related symptoms. It is important to talk with your healthcare provider if you notice one or more of these issues.
Some younger people, especially children and teens, taking Trikafta have developed cataracts while taking one of the ingredients of Trikafta, ivacaftor. Before starting Trikafta, younger people may need a baseline eye exam and follow-up exams while taking this drug. Children under 12 should not take Trikafta.
Considerations for talking to your doctor
Trikafta is broken down (metabolized) through a specific pathway in the body. It should not be taken with other drugs that may affect this pathway, called CYP3A inducers. Depending on what other drugs are being taken, your Trikafta dose may need to be changed.
Before starting Trikafta, tell your doctor about any and all drugs, herbs, or supplements you are taking. You should not drink grapefruit juice while taking Trikafta, as it may moderately inhibit CYP3A.
Before starting Trikafta tell your doctor if you:
- Have a history or liver or kidney problems
- Are taking any antibiotics, including rifabutin, rifampin, clarithromycin, erythromycin, or telithromycin
- Are taking any seizure medications, including carbamazepine, phenytoin, or phenobarbital
- Are taking St. John’s wort
- Are taking any antifungal medications, including ketoconazole, voriconazole, fluconazole, posaconazole, or itraconazole
- Are pregnant, planning to become pregnant, breastfeeding, or planning to breastfeed
Trikafta comes in fixed-dose tablet form. A tablet contains 100 mg of elexacaftor, 50 mg of tezacaftor, and 75 mg of ivacaftor. It is packaged with a second set of tablets that contain 150 mg of ivacaftor only.
Typically, 2 triple combination tablets are taken in the morning and 1 separate 150 mg ivacaftor tablet is taken in the evening. Both doses should be taken about 12 hours apart with a food that contains fat, like peanut butter, eggs, meat, nuts, or cheese.
It is important to take Trikafta exactly as prescribed. You should not stop or change your Trikafta dosage without talking to your doctor first. If you miss a dose, talk with your doctor.2
For more information, read the full prescribing information of Trikafta.