St. John’s Wort, Paxlovid, and More: 7 Xarelto Interactions to Be Aware Of

Xarelto (rivaroxaban) is a blood thinner medication that helps treat and prevent unwanted blood clots. It belongs to a class of blood thinners called direct-acting oral anticoagulants (DOACs).

DOACs like Xarelto are considered safer than other blood thinners, such as warfarin. They’re less likely to cause bleeding-related side effects and don’t require a special diet. They also have fewer drug interactions to worry about. But fewer doesn’t mean none — there are still some interactions it’s good to be aware of if you’re taking a DOAC.

Let’s take a look at seven Xarelto interactions and how to manage them. Keep in mind, this doesn’t include every possible interaction. It’s best to have your healthcare team review your medication list to check for any interactions before starting Xarelto.

1. Other blood thinners

Because Xarelto is a blood-thinning medication, taking it with other prescription blood thinners can raise your risk of bleeding. This includes other DOACs, such as Eliquis (apixaban) and anticoagulants such as warfarin and Lovenox (enoxaparin). It also includes antiplatelet medications, such as Plavix (clopidogrel). Low-dose aspirin is also considered a blood thinner, but we’ll cover it in the next section.

In most cases, you’ll only take one blood thinner at a time. But in some situations, you may need to take more than one type of blood thinner. In this case, be sure to follow your prescriber’s instructions. And let them know if you notice any signs of mild bleeding, such as frequent nosebleeds or bleeding when brushing or flossing your teeth. This could be an early sign that your blood isn’t clotting as well as it should.

If you notice blood in your urine or stool, you’re coughing or vomiting blood, or have a bruise that’s getting larger, seek emergency care. A more serious bleeding issue could be the cause.

2. NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) can also increase your bleeding risk. So it’s best to avoid combining them with blood thinners such as Xarelto.

Common over-the-counter (OTC) NSAIDs include ibuprofen (Advil, Motrin) and naproxen (Aleve). They’re also sometimes found in cold and flu medications, such as Advil Cold and Sinus (ibuprofen / pseudoephedrine).

Acetaminophen (Tylenol) is a safer OTC option for fever or pain if you’re taking Xarelto. You can also ask your pharmacist or prescriber for other NSAID alternatives that won’t increase your bleeding risk.

Good to know: Low-dose aspirin is an NSAID that’s OK to take with Xarelto. But you should only take a daily low-dose aspirin if your prescriber tells you to — it’s not recommended for everyone.

3. SSRIs and SNRIs

Some common antidepressants can also raise your risk of bleeding. And this risk goes up if you take them with Xarelto. This includes selective serotonin reuptake inhibitors (SSRIs) such as Zoloft (sertraline), escitalopram (Lexapro), and Prozac (fluoxetine). It also includes serotonin and norepinephrine reuptake inhibitors (SNRIs), such as Effexor XR (venlafaxine ER) and Cymbalta (duloxetine).

Be sure to let your prescriber know you’re taking an antidepressant if you’re starting Xarelto, or vice versa. In most cases, it’s still fine to take both medications. You’ll just need to keep a close eye out for signs of bleeding, especially in the first few months of taking them together. But in some cases, your prescriber may prefer an antidepressant that doesn’t interact with Xarelto.

4. Ketoconazole

The antifungal medication ketoconazole can interact with Xarelto. It can raise Xarelto levels, which can increase your risk of a bleed. It’s best to avoid combining ketoconazole and Xarelto. So be sure to let your prescriber know you’re taking Xarelto if you need medication for a fungal infection. They can choose an option that doesn’t interact.

Keep in mind that this interaction only applies to oral ketoconazole tablets. Ketoconazole cream is fine to use for skin-related fungal infections if you’re taking Xarelto.

5. Ritonavir and Paxlovid

Ritonavir (Norvir) is a common prescription treatment for HIV. It’s also an ingredient in Paxlovid (nirmatrelvir / ritonavir), an antiviral medication that treats COVID-19. Ritonavir can prevent the body from breaking down Xarelto. This raises Xarelto levels in the body and raises the risk of side effects, including bleeding.

Taking ritonavir or Paxlovid with Xarelto isn’t recommended. Your prescriber may suggest a different blood thinner for you. Or they may choose a different antiviral medication, if that’s an option.

6. St. John’s wort

St. John’s wort is a popular herbal supplement that people take to help with depression symptoms. But it interacts with a lot of prescription medications. And it can lower Xarelto levels in the body if they’re combined. This can make Xarelto less effective and put you at risk for blood clots.

Since St. John’s wort is an OTC supplement, it’s easy to forget to add it to your medication list. But interactions like these are possible with all OTC products, so it’s important to let your healthcare team know you’re taking them.

It’s best to avoid taking St. John’s wort with Xarelto. Talk to your prescriber about safer options to help support your mental health.

7. Certain anti-seizure medications

Some anti-seizure medications can interact with Xarelto. Phenytoin (Dilantin) and carbamazepine (Tegretol) can increase the breakdown of Xarelto in the body. This can lower Xarelto and increase your risk of developing blood clots.

It’s best to avoid combining Xarelto with these medications. If you’re already taking one of these anti-seizure medications, your prescriber will likely choose a different blood thinner for you. If you’re taking Xarelto and need to start an anti-seizure medication, they’ll likely choose one that’s less likely to have an interaction.

When should you seek medical advice about Xarelto interactions?

The best way to prevent Xarelto interactions is to review all of the medications and supplements you’re taking with your healthcare team before you start taking Xarelto. It’s equally important to ask your prescriber before starting anything new to make sure it’s safe while you’re taking Xarelto.

If you notice an increase in mild bleeding, that could be an early sign of an interaction. Let your prescriber know if this happens.

With more serious interactions, you may have severe bleeding or develop a blood clot. 

Signs of serious bleeding include:

• Blood in your urine or stool

• Coughing up or vomiting blood

• Severe stomach pain

• Cold, pale skin

• Confusion or dizziness

Signs and symptoms of a blood clot include:

• Pain, redness, and warmth in an arm or leg

• Sudden trouble breathing

• Chest pain

• Severe back pain

If you develop symptoms of a serious bleed or blood clot, call 911 or seek emergency medical care right away. These can be life-threatening issues if they aren’t treated.

Why trust our experts?

Written by:

Jill Barat, PharmD

Jill Barat, PharmD has nearly 10 years of experience as a pharmacist, including serving as the pharmacist in charge at an independent sterile and non-sterile compounding pharmacy. She also worked as the head of medical content for a telemedicine company.

Edited by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

Reviewed by:

Ferras Bashqoy, PharmD, BCCCP, BCPPS

Ferras Bashqoy, PharmD, BCCCP, BCPPS, is a clinical pharmacotherapy specialist in the Neonatal Intensive Care Unit (NICU) at Hassenfeld Children’s Hospital in New York City. His favorite part of the job is working with preterm newborns because they are strong and mighty despite their size.

Our editorial standards

Meet our experts