Asparaginase and Methotrexate: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Methotrexate
Asparaginase
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Decreased or elimination of methotrexate antineoplastic activity
Interaction Deep Dive
Asparaginase may diminish or abolish the effect of methotrexate on malignant cells. This effect persists as long as plasma asparagine levels are suppressed. Do not use methotrexate with, or following L-asparaginase, while asparagine levels are below normal. Alternatively, administration of L-asparaginase after methotrexate results in a synergistic effect. The extent to which these affect the overall effectiveness of established treatment protocols is not known1.
Why it happens (mechanism)
Asparaginase prohibits the cell replication necessary for methotrexate antineoplastic activity
Common questions
Can I take Asparaginase and Methotrexate together?
Decreased or elimination of methotrexate antineoplastic activity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Asparaginase and Methotrexate interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Asparaginase or Methotrexate need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Product Information: Erwinase intramuscular, intravenous injection, crisantaspase intramuscular, intravenous injection. Porton Biopharma Limited (per EMC), Porton Down, Salisbury, United Kingdom, 2021.
Keep reading about Methotrexate
Keep reading about Asparaginase
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist