Methotrexate Injection and Pristinamycin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Methotrexate Injection
Pristinamycin
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
Methotrexate toxicity (hemorrhage, anemia, septicemia)
Interaction Deep Dive
An interaction between methotrexate and pristinamycin was described1. Concurrent use apparently caused decreased methotrexate elimination which resulted in a greatly increased serum concentration.
Why it happens (mechanism)
Decreased methotrexate elimination
Literature reports
1 report — tap to read
a) A 13-year-old male patient had been treated for acute lymphoblastic leukemia 10 years previously with the EORTC protocol which included four high-dose methotrexate cycles 1. The patient had been in remission for 10 years when he developed a bone marrow relapse and was treated with a protocol that included methotrexate 5 g/m(2). He had been treated with pristinamycin 2 g daily for six days for a cutaneous Staphylococcus infection when the second methotrexate treatment block began, and the antibiotic was continued throughout the treatment block. During this treatment, elimination of methotrexate was decreased and serum concentrations increased, causing toxicity (grade 4 (WHO) oral mucositis, grade 4 hematologic toxicity). When the next treatment block was administered, methotrexate dose was reduced to 1 g/m(2) from 5 g/m(2), and methotrexate elimination was normal; no symptoms of toxicity were seen. Because this patient received methotrexate and experienced normal kinetics and no signs of toxicity both before and after the concurrent treatment with pristinamycin, it appears that a drug interaction between methotrexate and pristinamycin is a likely explanation. Pristinamycin is structurally similar to macrolide antibiotics which are known to interfere with hepatic metabolism of other drugs. Further study on this possible interaction is warranted.
Common questions
Can I take Methotrexate Injection and Pristinamycin together?
Methotrexate toxicity (hemorrhage, anemia, septicemia) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Methotrexate Injection and Pristinamycin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
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 Methotrexate Injection or Pristinamycin 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)
- Thyss A, Milano G, Renee N, et al: Severe interaction between methotrexate and a macrolide-like antibiotic (letter). J Natl Cancer Inst 1993; 85:582-583. PubMed
Keep reading about Methotrexate Injection
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