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Patients taking the anticoagulant (blood thinner) apixaban (ELIQUIS) should be aware that this drug has clinically important and potentially dangerous interactions with many other medications.
Apixaban belongs to a class of drugs called direct-acting oral anticoagulants (DOACs). The Food and Drug Administration first approved apixaban in 2012 to decrease the risk of stroke and systemic embolism (a blood clot lodged inside a blood vessel) in patients with nonvalvular atrial fibrillation (a...
Patients taking the anticoagulant (blood thinner) apixaban (ELIQUIS) should be aware that this drug has clinically important and potentially dangerous interactions with many other medications.
Apixaban belongs to a class of drugs called direct-acting oral anticoagulants (DOACs). The Food and Drug Administration first approved apixaban in 2012 to decrease the risk of stroke and systemic embolism (a blood clot lodged inside a blood vessel) in patients with nonvalvular atrial fibrillation (a common type of irregular heart rhythm not caused by a heart valve problem).[1] Subsequently, it has been approved to treat and reduce the risk of recurrence of deep vein thrombosis (a blood clot in a large vein, usually in the leg) and pulmonary embolism (which occurs when a blood clot blocks one of the arteries in the lungs). In patients who have undergone hip- or knee-replacement surgery, apixaban also is indicated to reduce the risk of deep vein thrombosis and pulmonary embolism. Apixaban is available in 2.5- or 5-milligram doses and is taken orally twice daily.
Based on a review of recent efficacy and safety data in the April 2024 issue of Worst Pills, Best Pills News, Public Citizen’s Health Research Group changed our designation of apixaban from Do Not Use to Limited Use.[2] We have designated all other DOACs, including rivaroxaban (XARELTO) and dabigatran (PRADAXA and generics), as Do Not Use because the various safety concerns associated with these drugs outweigh their benefits.
Drug-drug interactions for apixaban
Although interactions that occur when two drugs are taken at the same time (drug-drug interactions) are relatively common for all drugs, researchers estimate that most patients with atrial fibrillation who are treated with an oral anticoagulant will take at least one other drug that interacts with their blood thinner.[3] These interactions occur more often in the elderly, those who have several health conditions and those who take several medications concomitantly (at the same time).[4]
The two most concerning drug interactions for DOACs are with drugs that enhance the action of apixaban (causing bleeding) or diminish its effects (causing thrombotic events).[5] Importantly, although these are the main concerns for all DOACs, there are some differences between drugs in this class.[6] This article will discuss drug interactions only for apixaban.
Drugs that increase bleeding risk
All blood thinners can increase the risk of serious or life-threatening bleeding.[7],[8] This risk is particularly high when apixaban is taken at the same time with other drugs that also may cause bleeding, such as other anticoagulants (including warfarin [JANTOVEN and generics]) or antiplatelet drugs (such as aspirin [BAYER and generics]).[9] Additionally, several other drugs can inhibit (or slow) certain liver enzymes responsible for metabolizing apixaban, including nonsteroidal anti-inflammatory drugs, antidepressants and antifungals.[10] When such drugs are taken concomitantly with apixaban, they can increase the blood concentration of apixaban, leading to a higher risk of bleeding. Examples of oral drugs that may increase the bleeding risk of apixaban are shown in Table 1, below.
Table 1. Examples of Oral Drugs That May Increase the Risk of Apixaban Exposure and Bleeding[11],[12]
| Generic Name | Brand Name(s)† | Drug Class |
|---|---|---|
| amiodarone* | PACERONE and generics | Heart rhythm disorder drug |
| atazanavir | REYATAZ and generics | Antiviral drug for HIV infection |
| darunavir | PREZISTA and generics | Antiviral drug for HIV infection |
| dronedarone** | MULTAQ and generics | Heart rhythm disorder drug |
| fluconazole | DIFLUCAN and generics | Antifungal drug |
| itraconazole*** | SPORANOX, TOLSURA and generics | Antifungal drug |
| naproxen | ALEVE, ANAPROX DS, EC-NAPROSYN, NAPRELAN, NAPROSYN and generics | Nonsteroidal anti-inflammatory drug |
| posaconazole | NOXAFIL and generics | Antifungal drug |
| voriconazole | VFEND and generics | Antifungal drug |
| vortioxetine | TRINTELLIX | Selective serotonin reuptake inhibitor |
†Brand-name combination products that contain other active ingredients are not included.
*Designated as Limited Use by Public Citizen’s Health Research Group
**Designated as Do Not Use by Public Citizen’s Health Research Group
***Designated as Do Not Use Except For Serious Fungal Infection by Public Citizen’s Health Research Group
Drugs that increase the risk of thrombotic events
Some other drugs induce (or stimulate) liver enzymes, such as cytochrome P450 3A4, that reduce blood levels of apixaban, making the drug less effective in treating or preventing blood clots and strokes.[13],[14] Drugs that reduce apixaban’s effectiveness include certain antibiotics and seizure drugs as well as the supplement St. John’s wort. Notably, although certain drugs, such as the seizure drugs carbamazepine (CARBATROL, EPITOL, EQUETRO, TEGRETOL, TERIL and generics) and phenytoin (DILANTIN, PHENYTEK and generics), decrease blood levels of apixaban, this risk is much higher with other DOACs, such as dabigatran and rivaroxaban.[15]
Examples of oral drugs that may decrease blood levels of apixaban and increase the risk of thrombotic events are shown in Table 2, below.
Table 2. Examples of Oral Drugs That Decrease Exposure to Apixaban and Increase the Risk of Thrombotic Events[16],[17]
| Generic Name | Brand Name(s)† | Drug Class |
|---|---|---|
| apalutamide | ERLEADA | Prostate cancer drug |
| enzalutamide | XTANDI | Prostate cancer drug |
| primidone | MYSOLINE and generics | Antiseizure drug |
| rifampin | RIMACTANE and generics | Antibiotic/tuberculosis drug |
| topiramate*,** | EPRONTIA, QUDEXY XR, TOPAMAX, TROKENDI XR and generics | Antiseizure drug/migraine prevention drug |
†Brand-name combination products that contain other active ingredients are not included.
*Designated as Limited Use for epilepsy by Public Citizen’s Health Research Group
**Designated as Do Not Use for migraine prevention by Public Citizen’s Health Research Group
What You Can Do
If you are being treated with apixaban or need treatment with this drug or another blood thinner, review all your other medications with your clinician to identify potentially significant drug interactions. Never discontinue any anticoagulant without talking with your clinician first, because doing so can increase your risk of developing blood clots or stroke.
If you are taking a medication that interacts with apixaban, your clinician may recommend stopping or adjusting the dosage of the interacting drug or of apixaban or may advise you to take another drug, such as warfarin. Be aware that drugs not listed in this article also may have dangerous interactions with apixaban.
References
[1] Bristol-Myers Squibb. Label: apixaban (ELIQUIS). April 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202155s034lbl.pdf. Accessed July 9, 2024.
[2] The blood thinner apixaban (Eliquis): an update. Worst Pills, Best Pills News. April 2024. https://www.worstpills.org/newsletters/view/1589. Accessed July 9, 2024.
[3] Mar PL, Gopinathannair R, Gengler BE, et al. Drug interactions affecting oral anticoagulant use. Circ Arrhythm Electrophysiol. 2022;15(6):e007956.
[4] Ferri N, Colombo E, Tenconi M, et al. Drug-drug interactions of direct oral anticoagulants (DOACs): from pharmacological to clinical practice. Pharmaceutics. 2022;14(6):1120.
[5] Bristol Myers Squibb. Label: apixaban (ELIQUIS). April 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202155s034lbl.pdf. Accessed July 9, 2024.
[6] Ferri N, Colombo E, Tenconi M, et al. Drug-drug interactions of direct oral anticoagulants (DOACs): from pharmacological to clinical practice. Pharmaceutics. 2022;14(6):1120.
[7] Bristol Myers Squibb. Label: apixaban (ELIQUIS). April 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202155s034lbl.pdf. Accessed July 9, 2024.
[8] Wiggins BS, Dixon DL, Neyens RR, et al. Select drug-drug interactions with direct oral anticoagulants: JACC review topic of the week. J Am Coll Cardiol. 2020;75(11):1341-1350.
[9] Mar PL, Gopinathannair R, Gengler BE, et al. Drug interactions affecting oral anticoagulant use. Circ Arrhythm Electrophysiol. 2022;15(6):e007956.
[10] Terrier J, Gaspar F, Fontana P, et al. Drug-drug interactions with direct oral anticoagulants: practical recommendations for clinicians. Am J Med. 2021;134(8):939-942.
[11] Bristol-Myers Squibb. Label: apixaban (ELIQUIS). April 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202155s034lbl.pdf. Accessed July 9, 2024.
[12] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “apixaban.” Accessed July 9, 2024.
[13] Bristol Myers Squibb. Label: apixaban (ELIQUIS). April 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202155s034lbl.pdf. Accessed July 9, 2024.
[14] Terrier J, Gaspar F, Fontana P, et al. Drug-drug interactions with direct oral anticoagulants: practical recommendations for clinicians. Am J Med. 2021;134(8):939-942.
[15] Ferri N, Colombo E, Tenconi M, et al. Drug-drug interactions of direct oral anticoagulants (DOACs): from pharmacological to clinical practice. Pharmaceutics. 2022;14(6):1120.
[16] Bristol Myers Squibb. Label: apixaban (ELIQUIS). April 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202155s034lbl.pdf. Accessed July 9, 2024.
[17] IBM Micromedex. Drug interactions. http://www.micromedexsolutions.com/home/dispatch. Search term: “apixaban” Accessed July 9, 2024.
