Methotrexate and Apixaban (Eliquis) Drug Interaction
There is no clinically significant interaction between methotrexate and apixaban (Eliquis), and they can be safely used together with appropriate monitoring.
Evidence-Based Assessment
The available guidelines and research do not indicate any direct pharmacokinetic or pharmacodynamic interaction between methotrexate and apixaban. This is supported by:
The hepatitis C treatment guidelines from 2020 provide a comprehensive drug interaction table that shows apixaban (Eliquis) has no clinically significant interaction with the medications being reviewed 1.
While methotrexate has several well-documented drug interactions, particularly with medications like trimethoprim-sulfamethoxazole, NSAIDs, and certain antibiotics 2, there is no evidence suggesting a direct interaction with apixaban.
The British Association of Dermatologists guidelines mention interactions between methotrexate and several medications (including salicylates, NSAIDs, co-trimoxazole, trimethoprim, probenecid, phenytoin, retinoids, pyrimethamine, and frusemide), but do not list anticoagulants like apixaban 1.
Methotrexate's Known Drug Interactions
Methotrexate has several important drug interactions that clinicians should be aware of:
Antifolate medications: Trimethoprim-sulfamethoxazole and other antifolate antibiotics can cause severe bone marrow suppression when combined with methotrexate 2.
NSAIDs and salicylates: These can reduce renal elimination of methotrexate, potentially increasing toxicity 1, 3, 4.
Other medications: Probenecid, phenytoin, and certain other drugs can affect methotrexate levels through various mechanisms 1, 2.
Apixaban's Known Drug Interactions
Apixaban has its own set of interactions to be aware of:
P-glycoprotein (P-gp) inhibitors: Medications that inhibit P-gp (like telmisartan) may increase apixaban levels and bleeding risk 5.
Strong CYP3A4 inhibitors or inducers: These can significantly affect apixaban levels 1.
Other anticoagulants or antiplatelets: Combining apixaban with other blood thinners increases bleeding risk 1.
Clinical Management Recommendations
When prescribing both medications together:
Regular monitoring:
- Monitor complete blood count (CBC) and liver function tests as normally required for methotrexate
- Watch for any signs of unusual bleeding that might indicate increased anticoagulant effect
Patient education:
- Inform patients about signs of methotrexate toxicity (mouth ulcers, nausea, fatigue)
- Educate about bleeding signs that would require medical attention
Avoid adding other interacting medications:
- Be cautious about adding NSAIDs, which can interact with both medications
- Avoid trimethoprim-containing antibiotics with methotrexate
- Avoid strong P-gp inhibitors with apixaban
Special Considerations
Renal function: Both medications require dose adjustments in renal impairment. Monitor renal function regularly.
Elderly patients: May have reduced renal function and require closer monitoring.
Concomitant medications: Review the complete medication list for potential interactions with either drug.
While there is no direct interaction between methotrexate and apixaban, careful monitoring is still recommended due to the individual risk profiles of each medication and the potential for additive effects on parameters like liver function or blood counts.