8 Imbruvica Interactions and How to Manage Them

Imbruvica (ibrutinib) is a type of targeted therapy called a Bruton’s tyrosine kinase (BTK) inhibitor. The medication treats chronic lymphocytic leukemia (CLL) and Waldenström’s macroglobulinemia, two types of blood cancer. It also treats a condition called chronic graft-versus-host disease. 

Imbruvica is unique at what it does. Unlike many cancer medications, which are taken for a set period of time, Imbruvica is often taken indefinitely to keep cancer cells in check. And it comes in capsule, tablet, and liquid formulations, making it convenient to take at home. 

If you’ve been prescribed Imbruvica, it’s important to understand its potential interactions, as certain medications and foods can affect how well it works. Here, we’ll share tips on how to manage eight of the most common Imbruvica interactions.

Why Imbruvica interactions happen

Imbruvica is metabolized, or broken down, by a specific enzyme (protein) in the liver. If you take another medication that’s metabolized by the same enzyme, it can make Imbruvica less effective. The combination could also lead to extra side effects.

Research shows that about two-thirds of people who take Imbruvica also take medications that can interact with it. So if you’ve been prescribed Imbruvica, it’s important to familiarize yourself with these interactions to ensure you get the most benefit from your treatment.

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1. Antifungals

Antifungal medications treat fungal infections. Most fungal infections can be treated with a topical antifungal, but more serious infections may require an oral or injectable treatment.

Azole antifungals — such as fluconazole (Diflucan), ketoconazole (Nizoral), and itraconazole (Sporanox) — can slow the breakdown of several medications in the body. When these antifungals are paired with Imbruvica, they can cause a buildup of the cancer medication. This increases the risk of Imbruvica side effects, including:

• Nausea

• Diarrhea

• Muscle pain

• Fatigue or tiredness

• Bleeding or bruising

• Low red blood cell count

• Low white blood cell count

• Serious heart problems

If you have a fungal infection, the best option is to take an antifungal that doesn’t interact with Imbruvica. But this may not always be possible. Fortunately, there are ways to lower the risk of an interaction between Imbruvica and an azole antifungal.

If you only need to take an azole antifungal for a week or less, your oncologist may suggest taking a short break from Imbruvica until the infection clears. For longer antifungal treatments, it’s best to lower your dosage of Imbruvica while you’re taking the combination. But don’t worry: Clinical studies have found that lowering the dosage of Imbruvica doesn’t affect its effectiveness. The typical Imbruvica dosage for CLL is 420 mg daily, but the medication comes in different doses — ranging from 70 mg to 280 mg.

2. Antibiotics and antivirals

People with cancer have a high risk of developing fungal, bacterial, and viral infections — especially if they have a blood cancer such as CLL. Because of this, antifungals, antibiotics, and antiviral medications are commonly taken by people with cancer. 

Risk for more side effects

As with antifungals, some antibiotics and antivirals can increase the amount of Imbruvica in the body when taken together. These are the medications to watch out for.

Antibiotics:

• Clarithromycin (Biaxin XL)

• Erythromycin (Ery-Tab)

• Ciprofloxacin (Cipro)

Antivirals:

• Ritonavir (Norvir) and other ritonavir-containing medications, such as Paxlovid

• Nelfinavir (Viracept)

• Cobicistat (Tybost)

You can temporarily stop taking Imbruvica if you’re taking an antibiotic for a week or less. For longer-lasting antibiotic or antiviral treatments, though, Imbruvica dosage adjustments are usually necessary.

Risk for impaired effectiveness

Some antibiotics and antivirals can speed up the breakdown of medications in the body. Taking Imbruvica with these medications will likely lower the amount of Imbruvica in the body, making it less effective. 

Avoid taking these antibiotics and antivirals with Imbruvica:

• Rifampin

• Efavirenz (Sustiva)

• Etravirine (Intelence)

3. Other oral oncolytics

Imbruvica is a type of oral oncolytic (oral cancer medication). Other oral oncolytics can interact with Imbruvica.

In some cases, a lower dosage of Imbruvica (or both medications) may be needed to manage this type of interaction. That’s typically the case when Imbruvica is combined with the following medications that slow its breakdown:

• Ceritinib (Iressa)

• Crizotinib (Xalkori)

• Idelalisib (Zydelig)

• Imatinib (Gleevec)

Due to effectiveness concerns, these oral oncolytics shouldn’t be combined with Imbruvica at all:

• Lorlatinib (Lorbrena)

• Sotorasib (Lumakras)

• Apalutamide (Erleada)

• Enzalutamide (Xtandi)

• Dabrafenib (Tafinlar)

• Mitotane (Lysodren)

• Ivosidenib (Tibsovo)

4. Heart and blood pressure medications

Some people taking Imbruvica may experience serious heart-related side effects. These side effects include high blood pressure, irregular heart rhythms, and heart failure. High blood pressure is the most common, affecting nearly one-fifth of people who take Imbruvica.

These heart-related side effects can happen to anyone, but the risk is higher among people who have preexisting heart problems. So it’s important that heart issues are well managed before starting treatment with Imbruvica. However, be sure that you’re not taking any heart medications that interact with Imbruvica, including:

• Diltiazem (Cardizem)

• Verapamil (Verelan)

• Dronedarone (Multaq)

These heart medications can increase the amount of Imbruvica in the body. This interaction can significantly increase the risk of heart-related side effects if not managed properly.

If you take any of these heart medications, it’s important to discuss the best course of action with your oncologist and cardiologist before starting Imbruvica. They may recommend a lower dosage of Imbruvica or switching to a heart medication that doesn’t interact with the cancer treatment. Or they may suggest a different BTK inhibitor that’s less likely to cause these side effects, such as acalabrutinib (Calquence) or zanubrutinib (Brukinsa).

5. Anti-seizure medications

Several anti-seizure medications can speed up the breakdown of Imbruvica in the body. This interaction makes the cancer treatment less effective.

Imbruvica shouldn’t be combined with any of the following anti-seizure medications:

• Carbamazepine (Tegretol)

• Phenytoin (Dilantin)

• Cenobamate (Xcopri)

• Phenobarbital

• Primidone

Over half of people with seizure disorders continue to have seizures despite taking medication. So if your seizures are well managed with any of the anti-seizure medications listed above, it may be best to consider a different cancer treatment. Your oncologist and neurologist can help you understand the benefits and risks of switching to a different anti-seizure or cancer medication.

6. St. John’s wort

St. John’s wort is an over-the-counter supplement that’s marketed for managing depression. Similar to some of the medications listed above, St. John’s wort can speed up the breakdown of Imbruvica, making it less effective.

If you’re taking Imbruvica, it’s best to avoid St. John’s wort. Talk to a healthcare professional about alternative treatment options for depression. St. John’s wort is known to have many drug interactions, so it could also pose an issue with other medications you’re taking. Plus, whether St. John’s wort is actually effective for treating depression is still under debate.

7. Grapefruit

Grapefruit, grapefruit juice, and Seville oranges (also referred to as bitter or sour oranges) interact with many medications. And Imbruvica is one of them.

Consuming these citrus foods while taking Imbruvica increases your risk of experiencing side effects from the medication. So it’s best to avoid these foods altogether during treatment — especially in large or frequent quantities. Also, be sure to check for grapefruit and Seville orange in ingredient lists for juices, teas, and flavored waters.

8. Blood thinners

Imbruvica increases the risk of accidental bleeding. Bleeding problems happened in nearly 40% of people taking Imbruvica in clinical studies. Most cases of bleeding were mild, but serious internal bleeding also occurred. The risk of bleeding is higher if you’re taking a blood thinner with Imbruvica.

Talk to your oncologist about the risks and benefits of taking Imbruvica with a blood thinner. Blood thinners metabolized by the same enzyme as Imbruvica should be avoided. These include apixaban (Eliquis) and rivaroxaban (Xarelto). Warfarin (Coumadin, Jantoven) can also interact with Imbruvica and should be avoided.

Instead, consider safer blood thinner alternatives. Dabigatran (Pradaxa), betrixaban (Bevyxxa), and edoxaban (Savaysa) are all less likely to interact with Imbruvica. Ultimately, your prescriber will recommend the blood thinner that they think is the best option for you.

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Written by:

Vanessa Carranza, PharmD

Vanessa Carranza, PharmD, is a pharmacist who has dedicated her career to the advancement of medical education for healthcare providers, patients, and caregivers, most notably in the oncology space.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Sonja Jacobsen, PharmD, BCPS, BCOP

Sonja Jacobsen, PharmD, BCPS, BCOP,  is a clinical oncology pharmacy specialist currently practicing in Seattle. She has been practicing as a pharmacist since 2015 and is licensed to practice in Washington state and North Carolina.

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