Why Apixaban Drug Interactions Matter

Apixaban (brand name Eliquis) is a blood thinner that works by blocking Factor Xa, a clotting protein. Because it's processed in your body through specific enzymes (CYP3A4) and transport proteins (P-glycoprotein), other medications that affect these pathways can change how much Apixaban is in your blood — either too much (increasing bleeding risk) or too little (reducing protection against clots).

This guide covers the most important drug interactions you should know about, including prescription medications, over-the-counter drugs, supplements, and food or drink.

How Drug Interactions Work with Apixaban

Apixaban is metabolized primarily by an enzyme called CYP3A4 and transported by a protein called P-glycoprotein (P-gp). Drugs that inhibit or induce these pathways can alter Apixaban levels:

• CYP3A4/P-gp inhibitors slow down the breakdown of Apixaban → levels rise → higher bleeding risk
• CYP3A4/P-gp inducers speed up the breakdown of Apixaban → levels drop → reduced effectiveness, higher clot risk

Some interactions aren't about enzyme pathways at all — they involve medications that independently affect bleeding, amplifying the risk when combined with Apixaban.

Major Drug Interactions

The following medications have significant interactions with Apixaban and typically require dose adjustments or should be avoided entirely.

Strong CYP3A4 and P-gp Inhibitors (Increase Apixaban Levels)

These medications slow the breakdown of Apixaban, causing it to build up in your blood and significantly increasing bleeding risk:

• Ketoconazole (Nizoral) — antifungal
• Itraconazole (Sporanox) — antifungal
• Ritonavir (Norvir) — HIV protease inhibitor
• Clarithromycin (Biaxin) — antibiotic

When these drugs must be used with Apixaban, the dose is typically reduced by 50% (e.g., from 5 mg to 2.5 mg twice daily). If you're already on the 2.5 mg dose, your doctor may recommend avoiding these drugs altogether.

Strong CYP3A4 and P-gp Inducers (Decrease Apixaban Levels)

These medications speed up the breakdown of Apixaban, potentially making it ineffective at preventing clots:

• Rifampin (Rifadin) — antibiotic used for tuberculosis
• Carbamazepine (Tegretol) — seizure medication
• Phenytoin (Dilantin) — seizure medication
• St. John's Wort — herbal supplement

Avoid using these with Apixaban. Rifampin in particular can reduce Apixaban levels by roughly 50%, which could leave you unprotected against stroke or blood clots.

Other Anticoagulants (Increased Bleeding Risk)

Taking Apixaban with other blood thinners significantly increases the risk of major bleeding:

• Warfarin (Coumadin)
• Heparin (injectable)
• Enoxaparin (Lovenox)

Your doctor should not prescribe Apixaban alongside another anticoagulant unless there is a specific clinical reason (such as a brief overlap during transitions).

Antiplatelet Agents (Increased Bleeding Risk)

These medications prevent platelets from clumping together. Combining them with Apixaban raises bleeding risk:

• Aspirin — especially at doses above 81 mg/day
• Clopidogrel (Plavix)
• Prasugrel (Effient)

Some patients, particularly after a heart stent, may need both Apixaban and an antiplatelet agent temporarily. This decision should always be made by a cardiologist who can weigh the risks and benefits carefully.

Moderate Drug Interactions

These medications may modestly increase Apixaban levels or bleeding risk:

• Diltiazem (Cardizem) — calcium channel blocker, moderate CYP3A4 inhibitor. May increase Apixaban levels. Usually no dose adjustment needed, but monitoring is appropriate.
• Dronedarone (Multaq) — antiarrhythmic, P-gp inhibitor. May modestly increase Apixaban levels.
• Erythromycin (E-Mycin) — antibiotic, moderate CYP3A4 inhibitor.
• NSAIDs like Ibuprofen (Advil, Motrin) and Naproxen (Aleve) — don't change Apixaban levels but independently increase bleeding risk, especially GI bleeding.

SSRIs and SNRIs

Antidepressants in these classes — including Sertraline (Zoloft), Fluoxetine (Prozac), Venlafaxine (Effexor), and Duloxetine (Cymbalta) — can impair platelet function and may increase bleeding risk when combined with Apixaban. This doesn't mean you can't take them together, but your doctor should be aware.

Supplements and OTC Medications to Watch

Several common supplements and over-the-counter products can interact with Apixaban:

• St. John's Wort — This is the most dangerous herbal interaction. It's a strong CYP3A4 inducer and can significantly reduce Apixaban levels. Do not take St. John's Wort with Apixaban.
• Fish oil (Omega-3 fatty acids) — May have mild blood-thinning effects at high doses. Talk to your doctor before taking fish oil supplements.
• Vitamin E — High doses may increase bleeding risk.
• Ginkgo biloba — May affect platelet function and increase bleeding risk.
• Garlic supplements — Concentrated garlic supplements (not normal cooking amounts) may have antiplatelet effects.
• Aspirin — Even low-dose OTC Aspirin (81 mg) adds bleeding risk. Only take it with Apixaban if your doctor specifically tells you to.
• NSAIDs — Ibuprofen (Advil) and Naproxen (Aleve) are available over the counter and increase bleeding risk. Use Acetaminophen (Tylenol) for pain relief instead when possible.

Food and Drink Interactions

Compared to Warfarin, Apixaban has very few food interactions — which is one of its major advantages. However, there are a couple of things to be aware of:

• Grapefruit juice — A moderate CYP3A4 inhibitor that may modestly increase Apixaban levels. The clinical significance is uncertain, and occasional consumption is likely fine. However, drinking large amounts daily is not recommended.
• Alcohol — Heavy drinking can impair liver function and increase bleeding risk. Moderate alcohol consumption is generally acceptable, but discuss your intake with your doctor.
• No dietary restrictions — Unlike Warfarin, you do not need to limit Vitamin K–rich foods like spinach, kale, or broccoli while taking Apixaban.

What to Tell Your Doctor

Before starting Apixaban — or at every visit — make sure your doctor knows about:

• All prescription medications you take, including any recent additions or changes
• All over-the-counter medications, especially pain relievers (NSAIDs, Aspirin)
• All supplements and herbal products, particularly St. John's Wort, fish oil, Vitamin E, and Ginkgo biloba
• Any upcoming procedures — dental work, surgery, or spinal injections. Your doctor may need to temporarily pause Apixaban.
• Any new bleeding symptoms — unexplained bruising, blood in urine or stool, prolonged nosebleeds

Keeping an updated medication list on your phone or in your wallet is one of the simplest and most effective things you can do to prevent dangerous interactions.

Final Thoughts

Apixaban has fewer drug interactions than Warfarin, but that doesn't mean it's interaction-free. The biggest risks come from strong CYP3A4/P-gp inhibitors and inducers, other blood thinners, and common OTC pain relievers like Ibuprofen. Being honest and thorough with your healthcare providers about everything you take is the best way to stay safe.

For more on how Apixaban works, see our mechanism of action guide. For side effect information, read Apixaban side effects: what to expect. And if you need help finding the medication at a pharmacy near you, Medfinder can help.