Leucovorin and Glucarpidase: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Glucarpidase
Leucovorin
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
Reduced leucovorin exposure and reduced efficacy of leucovorin
Interaction Deep Dive
Coadministration of glucarpidase and leucovorin, a glucarpidase substrate, may result in reduced leucovorin exposure. If coadministration is required, do not administer leucovorin for at least 2 hours before or after glucarpidase administration21. Dose adjustments are not required for the first 48 hours following glucarpidase use. Administer leucovorin based on measured methotrexate concentration after 48 hours have passed from glucarpidase administration. Do not discontinue leucovorin use unless methotrexate concentration has been maintained for a minimum of 3 days below the leucovorin treatment threshold 2.
Why it happens (mechanism)
Unknown
Literature reports
1 report — tap to read
a) A study of high-dose methotrexate (greater than or equal to 1 g/m(2)), leucovorin, and IV glucarpidase (50 units/kg) in cancer patients revealed a decrease in leucovorin AUC and Cmax. Glucarpidase was administered 2 hours prior to leucovorin which resulted in a 33% reduction in leucovorin AUC and a 52% reduction in Cmax. The AUC and Cmax of the leucovorin active metabolite, (6S)-5-methlytetrahydrofolate, were also reduced by 92% and 93%, respectively 2.
Common questions
Can I take Leucovorin and Glucarpidase together?
Reduced leucovorin exposure and reduced efficacy of leucovorin Always confirm with your pharmacist or prescriber before making any change.
How serious is the Leucovorin and Glucarpidase 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Leucovorin or Glucarpidase 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 (2)
- Product Information: VYKOURA™ intramuscular, intravenous injection, leucovorin calcium intramuscular, intravenous injection. Avyxa Pharma LLC (per FDA), Denville, NJ, 2026.
- Product Information: VORAXAZE(R) IV injection, glucarpidase IV injection. BTG International Inc. (per FDA), West Conshohocken, PA, 2012.
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