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9 Rinvoq Interactions to Be Aware of — From Paxlovid to Grapefruit

Cassandra Pardini, PharmD, MSDaphne Berryhill, RPh
Published on October 12, 2023

Key takeaways:

  • Rinvoq (upadacitinib) is a Janus kinase inhibitor that treats a variety of inflammatory health conditions. It interacts with many medications, over-the-counter products, and supplements.

  • Rinvoq interacts with medications and foods that affect a protein in charge of how it breaks down in the body. Examples include Paxlovid (nirmatrelvir / ritonavir), grapefruit, and St. John’s wort. These interactions can lead to more intense Rinvoq side effects or a drop in its effectiveness.

  • You should avoid live vaccines, such as the intranasal flu vaccine and the measles, mumps, and rubella vaccine, while taking Rinvoq. They may cause an accidental infection.

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Custom graphic showcasing the types of drugs that interact with Rinvoq. In the center is a purple Rinvoq pill on a green circle. On the left, on a red circle, is a half of a grapefruit. On the right, on a red circle, is a pink oblong pill. The circles are connected with a broken zig-zag line.
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Rinvoq (upadacitinib) is a medication that’s FDA approved to treat several inflammatory health conditions, including rheumatoid arthritis, eczema, and ulcerative colitis. A type of Janus kinase (JAK) inhibitor, it decreases inflammation by calming down your immune system. Many people benefit from it.

It has a few precautions to keep in mind, though. Since it’s a newer medication, Rinvoq is only available as a brand-name product. A lower-cost generic isn’t available yet. And although it’s effective, Rinvoq isn’t always used right away. It’s usually a next-choice option for people who haven’t had luck with other treatments.

Rinvoq also has drug interactions to consider. It’s broken down (metabolized) by a specific enzyme (protein) in your body — called CYP3A4. Many medications and some foods can impact Rinvoq’s safety and effectiveness by affecting how this enzyme works. So, if you find yourself with a prescription for this JAK inhibitor, it’s important to keep the top nine Rinvoq interactions in mind.

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1. Certain antifungals

If you’ve ever had ringworm, nail fungus, or a yeast infection, you may have used an antifungal to treat it. Many antifungals are available over the counter (OTC), while others are only available with a prescription.

Some antifungals can block the enzyme that breaks down Rinvoq. In turn, your body can’t metabolize Rinvoq as efficiently as it normally would. This can cause the medication to stay in your body longer than normal, increasing the risk of Rinvoq side effects. 

Azole antifungals are especially prone to this interaction. Some popular examples of azole antifungals are fluconazole (Diflucan), ketoconazole, and itraconazole (Sporanox).

If you need an antifungal medication while you’re taking Rinvoq, make sure to loop in your pharmacist and healthcare provider. This is important even if you only need the antifungal for a short period of time. They may want to decrease your Rinvoq dose while you’re taking the antifungal.

Good to know: This interaction is more worrisome with antifungals that are swallowed or injected into your body. Topical antifungals are less of an issue.

2. Verapamil and diltiazem

Verapamil (Verelan) and diltiazem (Cardizem, Cartia XT) are calcium channel blockers. They work by relaxing your blood vessels and slowing down your heart rate. Both medications treat chest pain and high blood pressure, but verapamil can also manage abnormal heart rhythms.

This pair of medications interacts with Rinvoq in a similar way as antifungals. They prevent enzymes from breaking down Rinvoq normally. This increases the risk of side effects from the medication. Keep an eye out for new or worsening nausea, headache, or skin rashes if you’re taking these medications with Rinvoq.

If you’re taking verapamil or diltiazem for a heart-related health condition, your healthcare provider will likely decrease your dose of Rinvoq. They may even avoid prescribing it altogether.

3. Medications that contain ritonavir

Ritonavir (Norvir) is an antiviral medication. It’s typically used in combination with other medications to treat HIV. It’s also a component of Paxlovid (nirmatrelvir / ritonavir), an antiviral that’s FDA approved to treat COVID-19 in certain people.

Ritonavir acts as a “booster” to make the antiviral it’s paired with more effective. It does this by blocking its breakdown so the antiviral stays in the body longer. Ritonavir can also “boost” the amount of Rinvoq in your body. But this would increase the risk of Rinvoq side effects without any extra benefits.

If you need to combine Rinvoq and a ritonavir-containing medication, your healthcare provider will likely lower your Rinvoq dosage. They’ll also want to monitor you extra closely for side effects. Depending on the situation, you may need to avoid this combination altogether.

4. Grapefruit

Grapefruit may be a healthy part of your diet. But you should avoid it if you’re taking Rinvoq. Food and drinks containing grapefruit make it harder for your body to break down Rinvoq. This, again, leads to an increased risk of side effects. 

All quantities of grapefruit can interact with Rinvoq. But this interaction is more concerning when you consume larger amounts of grapefruit. If grapefruit is one of your favorite foods, ask your healthcare provider if you can still enjoy small amounts of it from time to time. 

5. Certain antibiotics, such as clarithromycin and rifampin

Similar to some antifungals, a handful of antibiotics can interact with Rinvoq. 

Clarithromycin (Biaxin XL), a macrolide antibiotic, is one example. This medication interferes with the enzyme that breaks down Rinvoq. This can raise the amount of Rinvoq in your body. If possible, your healthcare provider will prescribe a different antibiotic that doesn’t interact with Rinvoq. But if clarithromycin is the best or only option for your infection, they’ll likely lower your dose of Rinvoq while you’re taking the two together.

Rifampin (Rifadin) is another antibiotic that interacts with Rinvoq. It’s best known for its ability to treat tuberculosis. This antibiotic also interacts with Rinvoq, but in a different way: It amplifies the effect of the CYP3A4 enzyme. This causes Rinvoq to leave your body faster, which makes it less effective. So avoid taking Rinvoq and rifampin together.

These aren’t the only antibiotics that interact with Rinvoq. Other antibiotics that interact with it include ciprofloxacin (Cipro) and erythromycin (Ery-Tab).

6. Phenobarbital, carbamazepine, and phenytoin

Phenobarbital (Sezaby), carbamazepine (Tegretol), and phenytoin (Dilantin, Phenytek) are medications that manage seizures.

Because of how they work, these antiseizure medications make Rinvoq less effective. They amplify the effects of CYP3A4 and cause it to break down Rinvoq faster than normal. But between the three, phenytoin and carbamazepine are thought to cause a much stronger interaction. 

You should avoid taking these medications at the same time as Rinvoq as a precaution. Seizures and autoimmune conditions can both be tricky to treat, so your healthcare provider can work with you to decide how to adjust your medication regimen. They’ll likely recommend a different medication for your inflammation or seizures to avoid this combination.

7. St. John’s wort

If you have ever visited the supplement aisle at your pharmacy or grocery store, you may have seen St. John’s wort. It’s a dietary supplement that’s marketed to treat mood disorders, especially depression.

Even though it’s available OTC, St. John’s wort interacts with a lot of other medications — including Rinvoq. It causes Rinvoq to be broken down faster. Avoid St. John’s wort if you’re taking Rinvoq.

This doesn’t mean you should skip out on depression or anxiety treatment, however. Many mental health medications don’t interact with Rinvoq. If you’re experiencing symptoms of depression or anxiety, talk to your healthcare provider about safe and effective treatment options for your situation.

8. Live vaccines

Rinvoq interacts with “live virus” vaccines. Examples include the measles, mumps, and rubella vaccine and the nasal spray flu vaccine. 

Rinvoq intentionally weakens your immune system. This is how it treats autoimmune disorders. But it also hinders your ability to fight infections. Live vaccines introduce your body to a weakened version of a virus, which could lead to an infection. If your immune system isn’t as strong as it could be, live vaccines may not be safe for you to receive.

To be safe, you should avoid receiving live vaccines while taking Rinvoq. Talk to your healthcare provider to make sure that all your vaccinations are up to date before starting Rinvoq.

9. Some medications that weaken your immune system

Sometimes, more than one immune-lowering medication is needed to keep inflammation in check. Your healthcare provider may recommend taking one of these medications with Rinvoq, such as methotrexate. But Rinvoq shouldn’t be taken with more potent medications, like azathioprine (Imuran), autoimmune biologics, or other JAK inhibitors. This could weaken your immune system too much.

When should I contact my healthcare provider about a Rinvoq interaction?

You should talk to your pharmacist and healthcare provider about your medications before starting Rinvoq. This will help them catch any problematic interactions before they happen. Supplying them with an updated medication list will help streamline this process; make sure all your prescription medications, OTC products, and supplements make it onto the list.

This isn’t the only time you should reach out to them. You should feel empowered to tell them about any bothersome symptoms that appear while you’re taking Rinvoq. They can check to see if an interaction is at fault. But if you suddenly develop trouble breathing, severe stomach pain, or chest pain, seek emergency care right away.

The bottom line

Many medications interact with Rinvoq (upadacitinib). Some interactions worsen Rinvoq’s side effects, while others make it less effective. Examples of Rinvoq interactions include certain antifungals and antibiotics, medications containing ritonavir, and heart medications like verapamil. It’s important to tell your healthcare provider and pharmacist about all the medications and supplements you take before starting Rinvoq.

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Why trust our experts?

Cassandra Pardini, PharmD, MS
Cassandra Pardini has been a freelance medical writer for 7 years. In that time, she has concentrated on publishing articles on medication-related information for healthcare professionals and patients.
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.
Daphne Berryhill, RPh
Daphne Berryhill, RPh, has two decades of experience as a clinical pharmacist. She spent most of her career in the Chicago area practicing in-home infusion.
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Fleet, J. L., et al. (2013). Comparing two types of macrolide antibiotics for the purpose of assessing population-based drug interactions. British Medical Journal Open.

Loos, N. H. C., et al. (2022). The mechanism-based inactivation of CYP3A4 by ritonavir: What mechanism? International Journal of Molecular Sciences.

Mar, P. L., et al. (2022). Drug interactions affecting antiarrhythmic drug use. Circulation: Arrhythmia and Electrophysiology.

National Institutes of Health. (2023). Drug-drug interactions between ritonavir-boosted nirmatrelvir (Paxlovid) and concomitant medications.

Padda, I. S., et al. (2023). Upadacitinib. StatPearls.

Roby, C.A., et al. (2000). St John's wort: Effect on CYP3A4 activity. Clinical Pharmacology & Therapeutics.

U.S. Food and Drug Administration. (2021). Grapefruit juice and some drugs don’t mix.

U.S. Food and Drug Administration. (2023). For healthcare professionals | FDA’s examples of drugs that interact with CYP enzymes and transporter systems.

GoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our editorial guidelines.

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