Levoleucovorin and Glucarpidase: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Glucarpidase
Levoleucovorin
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
Reduced levoleucovorin plasma concentrations
Interaction Deep Dive
Coadministration of glucarpidase and levoleucovorin, a substrate for glucarpidase, may result in decreased levoleucovorin plasma concentrations. Although the interaction has not been studied with levoleucovorin, both the AUC and Cmax of leucovorin were reduced in cancer patients receiving high-dose methotrexate, leucovorin rescue regimen, and IV glucarpidase, when glucarpidase was administered 2 hours prior to leucovorin. If coadministration is required, do not administer levoleucovorin for at least 2 hours before or after glucarpidase administration. Dose adjustments are not required for the first 48 hours following glucarpidase use. After 48 hours, administer continued levoleucovorin regimen based on pre-glucarpidase methotrexate concentration. Do not discontinue levoleucovorin use unless methotrexate concentration has been maintained for a minimum of 3 days below the levoleucovorin treatment threshold1.
Why it happens (mechanism)
Levoleucovorin being a substrate of glucarpidase
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 1.
Common questions
Can I take Levoleucovorin and Glucarpidase together?
Reduced levoleucovorin plasma concentrations Always confirm with your pharmacist or prescriber before making any change.
How serious is the Levoleucovorin and Glucarpidase interaction?
It is rated moderate. Can be significant — usually manageable with 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.
Questions for your pharmacist
- Does my dose of Levoleucovorin 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 anything you'd monitor while I'm on both?
References (1)
- Product Information: VORAXAZE(R) IV injection, glucarpidase IV injection. BTG International Inc. (per FDA), West Conshohocken, PA, 2012.
Keep reading about Glucarpidase
Keep reading about Levoleucovorin
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