10 Trikafta Interactions and How to Manage Them

In 2019, the FDA approved Trikafta (elexacaftor / tezacaftor / ivacaftor) as the first triple combination treatment option for the most common cystic fibrosis (CF) mutation. Trikafta can help people living with CF, but it can also interact with other medications — and the list is long. Trikafta also interacts with certain foods, including grapefruit.

It’s important to understand which medications, supplements, and foods can affect Trikafta. Certain combinations should be avoided, while others need to be managed. In some cases, you may need to take Trikafta on a different dosage schedule.

Below, we’ll cover 10 important Trikafta interactions. This isn’t a comprehensive list. Check with your healthcare team before starting new medications or supplements with Trikafta.

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1. Rifampin

Rifampin (Rifadin) is an antibiotic that’s used to treat tuberculosis. It’s also used to prevent meningococcal infections from spreading. If taken together with Trikafta, it can greatly lower the levels of Trikafta in the body. This means Trikafta may not work as well for you. So taking rifampin while you’re taking Trikafta isn’t recommended.

2. Seizure medications like carbamazepine

Some seizure medications interact with Trikafta. A few examples include carbamazepine (Tegretol), phenytoin (Dilantin), and phenobarbital. These medications speed up the breakdown of Trikafta in your liver, which leads to less of it in your body. If this happens, your CF symptoms could get worse. It’s not recommended to take these medications with Trikafta.

These aren’t the only seizure medications that may cause an interaction. If you’re taking medication for seizures, tell your prescriber before starting Trikafta.

3. St. John’s wort

St. John’s wort is an over-the-counter herbal supplement that can interact with many medications, including Trikafta. It’s often used for depression, but people take it for other health conditions as well. St. John’s wort can cause the liver to break down Trikafta faster, making it less effective.

Because of this interaction, it’s not recommended to take St. John’s wort with Trikafta. Your prescriber can help you find a safer alternative.

4. Antifungals like ketoconazole

Some medications taken to treat fungal infections may interact with Trikafta. Examples of antifungals that interact with it include:

• Itraconazole (Sporanox)

• Fluconazole (Diflucan)

• Ketoconazole

• Posaconazole (Noxafil)

• Voriconazole (Vfend)

You may need to take one of these medications to treat infections such as oral thrush, a vaginal yeast infection, or a bloodstream infection. But they can block proteins in your liver that help clear Trikafta from your body. This can cause higher Trikafta levels, which increases the risk of side effects.

If you need to take an antifungal that interacts with Trikafta, your prescriber may recommend Trikafta on a different dosage schedule. Once you’re finished with your antifungal course, ask your prescriber about when to resume taking your usual dose.

5. Macrolide antibiotics like clarithromycin

If you’re prescribed a macrolide antibiotic, check if it interacts with Trikafta. Some macrolides, such as clarithromycin and erythromycin (Ery-Tab), can increase the amount of Trikafta in your body. Certain macrolides may interact more strongly than others.

A common macrolide antibiotic that’s prescribed for people living with CF is azithromycin (Zithromax). This macrolide doesn’t appear to interfere with proteins that break down Trikafta. It isn’t expected to cause issues.

Depending on your infection, your prescriber might recommend an alternative antibiotic. Or they might change your Trikafta dosage schedule while treating your infection. Be sure to follow their instructions to avoid this potential interaction.

6. Sulfonylureas like glipizide, and other diabetes medications

Sulfonylureas are a group of oral medications used to treat Type 2 diabetes. Common examples include glimepiride (Amaryl), glipizide, and glyburide (Glynase, Diabeta). Some sulfonylureas can interact with Trikafta.

For example, ivacaftor (part of Trikafta) can block proteins that break down glimepiride and glipizide. This results in higher levels in the body. Trikafta can also prevent transporting glyburide to the liver, where it’s broken down. These interactions can increase sulfonylurea levels in the body. This raises the risk of side effects such as low blood glucose (sugar).

Similar diabetes medications, such as nateglinide, can also interact with Trikafta. So it’s best to have your care team review your medication list for potential interactions. Some interactions can be managed with dosage adjustments or close monitoring.

7. Warfarin

Warfarin (Jantoven) is a blood thinner that’s used to prevent and treat blood clots. Taking it alongside Trikafta could cause warfarin to build up in your body. This could put you at a higher risk for bleeding.

If you’re taking warfarin, your prescriber will want to check your international normalized ratio (INR) more often. An INR is a blood test that shows how well your blood can clot. When it’s too high, you could be at a higher risk for bleeding.

Be sure to get your bloodwork done on time if you take warfarin. This is especially important if you’re taking Trikafta or another medication that could interact with it.

8. Digoxin

Studies have shown that Trikafta can also interact with digoxin (Lanoxin). Digoxin is used to treat heart failure and atrial fibrillation. When taken together, Trikafta can increase digoxin levels in your body. And too much digoxin could cause side effects, such as changes in heart rate and vomiting. Digoxin toxicity is also possible.

Your prescriber can check the amount of digoxin in your body with a blood test. Make sure to keep up with all your follow-up appointments. Tell them if you notice new or worsening side effects. These include nausea and vomiting, changes in your vision, and a fluttering heart rate.

9. Transplant medications like tacrolimus

Trikafta can interact with medications used to prevent organ transplant rejection. Examples of these medications include:

• Cyclosporine (Sandimmune, Neoral, Gengraf)

• Sirolimus (Rapamune)

• Tacrolimus (Prograf)

Certain pumps in our gut play a role in how much medication gets absorbed into our bloodstream. Trikafta can block some of these pumps. This can cause your body to absorb higher amounts of some transplant medications, raising your risk for side effects.

Trikafta can interact with these medications, but that doesn’t mean you can’t take them together. Your care team may want to monitor your medication levels closely to make sure your transplant medication doses are safe and effective for you.

10. Grapefruit and grapefruit juice

In addition to medications, Trikafta can also interact with grapefruit. Substances in grapefruit can block Trikafta from breaking down in your body. Taking Trikafta with grapefruit or grapefruit juice may increase levels of Trikafta. This would lead to side effects.

The manufacturer of Trikafta recommends avoiding grapefruit juice while you’re taking it. If you have questions about this, ask your prescriber.

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Written by:

Kristianne Hannemann, PharmD

Kristianne Hannemann, PharmD, is a licensed pharmacist in California. She has been a retail pharmacy manager and staff pharmacist for over 7 years and has contributed drug information content to different health companies.

Edited by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

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