Key takeaways:
Xarelto (rivaroxaban) is a prescription blood thinner. It can interact with other blood thinners, nonsteroidal anti-inflammatory drugs (NSAIDs), and some antidepressants. It’s best to avoid taking Xarelto with these medications unless your prescriber OKs it.
Other Xarelto interactions include ketoconazole, Norvir (ritonavir), and Paxlovid (nirmatrelvir / ritonavir). These medications can increase Xarelto levels in the body, which can raise your risk of bleeding.
Some anti-seizure medications and St. John’s wort supplements can make Xarelto less effective, which can raise your risk of blood clots.
Save on related medications
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).
Xarelto and other DOACs are generally considered safer than other blood thinners, such as warfarin (Coumadin, Jantoven). They’re less likely to cause bleeding-related side effects overall 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 Xarelto.
Xarelto interactions at a glance
Below is an overview of medications that may interact with Xarelto:
Other anticoagulants and antiplatelet medications (blood thinners)
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Certain antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs)
Norvir (ritonavir)
Paxlovid (nirmatrelvir / ritonavir)
Alcohol
Rifampin (Rifadin)
Pepto Bismol (bismuth subsalicylate)
Keep in mind, this list 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. It’s also a good idea to check with your prescriber or pharmacist before taking any over-the-counter (OTC) medications or supplements with Xarelto.
Let’s take a closer look at eight Xarelto interactions and their risks.
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 unusual bruising, frequent nosebleeds, or bleeding when brushing or flossing your teeth. These could be early signs 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
NSAIDs can also increase your bleeding risk. So it’s best to avoid combining them with blood thinners such as Xarelto.
Common 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). Even some medications for upset stomach, such as Pepto-Bismol and Alka Seltzer, contain NSAIDs you may not be aware of.
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 SSRIs such as Zoloft (sertraline), Lexapro (escitalopram), and Prozac (fluoxetine). It also includes SNRIs, such as Effexor XR (venlafaxine ER) and Cymbalta (duloxetine).
Xarelto FAQs: Learn more about how long it takes Xarelto to work and how long you’ll need to take it.
Xarelto side effects: Learn more about possible Xarelto side effects, how to manage them, and when to seek medical care.
Signs of bleeding: How to recognize the signs and symptoms of internal bleeding, and when to seek help.
Be sure to let your prescriber know you’re taking an antidepressant before 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 oral 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.
Good to know: 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. Norvir and Paxlovid
Norvir is a common prescription treatment for HIV. Ritonavir (the active ingredient in Norvir) is also an ingredient in Paxlovid, 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 Norvir, Paxlovid, or other medications that contain ritonavir 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. 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 many 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. Dilantin (phenytoin) and Tegretol (carbamazepine) can increase the breakdown of Xarelto in the body. This can lower Xarelto levels 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.
8. Alcohol
It’s best to avoid or limit alcohol while taking Xarelto. There’s no direct interaction between Xarelto and alcohol. But heavy alcohol use increases the risk of serious bleeding while taking Xarelto. A drink or two now and then shouldn’t be a problem. But keep in mind that even a moderate amount of alcohol can thin your blood and make bleeding more likely.
If you’re unsure how much alcohol is safe for you, it’s a good idea to check in with your healthcare team. They can also provide support to help you cut back on your drinking if you’re having trouble doing so on your own.
Frequently asked questions
No, you don’t have to avoid any specific foods with Xarelto. Unlike warfarin, foods rich in vitamin K won’t interfere with how Xarelto works. But it’s a good idea to limit grapefruit and grapefruit juice while you’re taking Xarelto. Large amounts of grapefruit may raise Xarelto levels in the body. It’s also good to know that adults should take Xarelto doses of 15 mg or higher with food — preferably with your largest meal of the day. This helps your body absorb the medication better.
Research shows that taking Xarelto in the evening leads to higher and longer-lasting levels of Xarelto in the bloodstream than morning doses. This makes taking it at night beneficial since studies show that the risk of dangerous blood clots is often higher early in the morning. So taking Xarelto in the evening helps ensure you’re protected from blood clots during the higher-risk early morning hours.
There are no vitamins that directly interact with Xarelto. But large amounts of vitamin E can increase your bleeding risk. And if you’re taking Xarelto, this risk could be even higher. While most vitamins are safe when taken according to the label directions, it’s always a good idea to check with your healthcare team before starting any new supplements while taking Xarelto. They can review the ingredients and amounts to make sure the product is safe for you.
No, you don’t have to avoid any specific foods with Xarelto. Unlike warfarin, foods rich in vitamin K won’t interfere with how Xarelto works. But it’s a good idea to limit grapefruit and grapefruit juice while you’re taking Xarelto. Large amounts of grapefruit may raise Xarelto levels in the body. It’s also good to know that adults should take Xarelto doses of 15 mg or higher with food — preferably with your largest meal of the day. This helps your body absorb the medication better.
Research shows that taking Xarelto in the evening leads to higher and longer-lasting levels of Xarelto in the bloodstream than morning doses. This makes taking it at night beneficial since studies show that the risk of dangerous blood clots is often higher early in the morning. So taking Xarelto in the evening helps ensure you’re protected from blood clots during the higher-risk early morning hours.
There are no vitamins that directly interact with Xarelto. But large amounts of vitamin E can increase your bleeding risk. And if you’re taking Xarelto, this risk could be even higher. While most vitamins are safe when taken according to the label directions, it’s always a good idea to check with your healthcare team before starting any new supplements while taking Xarelto. They can review the ingredients and amounts to make sure the product is safe for you.
The bottom line
Xarelto (rivaroxaban) is a prescription blood thinner medication. Some Xarelto interactions can raise your risk of bleeding. This includes other blood thinners, nonsteroidal anti-inflammatory drugs (NSAIDs), and some antidepressants. Alcohol may also increase your bleeding risk while taking Xarelto. You should avoid these combinations unless you have a healthcare professional’s OK.
Combining Xarelto with oral ketoconazole, ritonavir (Norvir), or Paxlovid (nirmatrelvir / ritonavir) can also raise your risk of bleeding. It’s best to avoid taking these medications together.
St. John’s wort supplements and certain anti-seizure medications can lower Xarelto levels in the body. This can make Xarelto less effective and raise your risk for blood clots. So these combinations aren’t recommended.
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References
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Grześk, G., et al. (2021). The clinical significance of drug–food interactions of direct oral anticoagulants. International Journal of Molecular Sciences.
Kirchhof, P., et al. (2020). Impact of modifiable bleeding risk factors on major bleeding in patients with atrial fibrillation anticoagulated with rivaroxaban. Journal of the American Heart Association.
Macleods Pharmaceuticals. (2025). Rivaroxaban tablet, film coated [package insert].
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Rohr, B. S., et al. (2021). Perpetrator characteristics of azole antifungal drugs on three oral Factor Xa inhibitors administered as a microdosed cocktail. Clinical Pharmacokinetics.
Scheer, F. A. J. L., et al. (2014). Human circadian system causes a morning peak in prothrombotic plasminogen activator inhibitor-1 (PAI-1) independent of the sleep/wake cycle. Blood.
